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Sample records for basophilic leukaemia cells

  1. Klinefelter syndrome and acute basophilic leukaemia--case report.

    Science.gov (United States)

    Ljubić, Nives; Lang, Nada; Skelin, Ika Kardum; Lasan, Ruzica; Dominis, Mara; Perković, Leila; Zupanić-Krmek, Dubraka; Grgurević-Batinica, Anita

    2010-06-01

    Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

  2. Use of humanised rat basophilic leukaemia cell line RS-ATL8 for the assessment of allergenicity of Schistosoma mansoni proteins.

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    Daniel Wan

    2014-09-01

    Full Text Available Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised. A better insight into the basic mechanisms of anti-parasite immunity could be gained from a genome-wide characterisation of such S. mansoni allergens. This would have repercussions on our understanding of allergy and the development of safe and efficacious vaccinations against helminthic parasites.A complete medium- to high-throughput amenable workflow, including important quality controls, is described, which enables the rapid translation of S. mansoni proteins using wheat germ lysate and subsequent assessment of potential allergenicity with a humanised Rat Basophilic Leukemia (RBL reporter cell line. Cell-free translation is completed within 90 minutes, generating sufficient amounts of parasitic protein for rapid screening of allergenicity without any need for purification. Antigenic integrity is demonstrated using Western Blotting. After overnight incubation with infected individuals' serum, the RS-ATL8 reporter cell line is challenged with the complete wheat germ translation mixture and Luciferase activity measured, reporting cellular activation by the suspected allergen. The suitability of this system for characterization of novel S. mansoni allergens is demonstrated using well characterised plant and parasitic allergens such as Par j 2, SmTAL-1 and the IgE binding factor IPSE/alpha-1, expressed in wheat germ lysates and/or E. coli. SmTAL-1, but not SmTAL2 (used as a negative control, was able to activate the basophil reporter cell line.This method offers an accessible way for assessment of potential allergenicity of anti-helminthic vaccine candidates and is suitable for medium- to high-throughput studies using infected individual sera. It is also suitable for the study of the basis of allergenicity of helminthic proteins.

  3. Measuring histamine and cytokine release from basophils and mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

    2014-01-01

    Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ...

  4. Adherence of human basophils to cultured umbilical vein endothelial cells.

    OpenAIRE

    1988-01-01

    The mechanism by which circulating human basophils adhere to vascular endothelium and migrate to sites of allergic reactions is unknown. Agents have been identified which stimulate the adherence of purified basophils to cultured human umbilical vein vascular endothelial cells (HuVEC). Treatment of HuVEC with interleukin 1, tumor necrosis factor (TNF), bacterial endotoxin, and 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in time and dose-dependent increases of adhesiveness for basophils...

  5. Mast cells and basophils in cutaneous immune responses.

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    Otsuka, A; Kabashima, K

    2015-02-01

    Mast cells and basophils share some functions in common and are generally associated with T helper 2 (Th2) immune responses, but taking basophils as surrogate cells for mast cell research or vice versa for several decades is problematic. Thus far, their in vitro functions have been well studied, but their in vivo functions remained poorly understood. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for mast cells and basophils in several skin disorders. Newly developed mast cell-deficient mice provided evidence that mast cells initiate contact hypersensitivity via activating dendritic cells. In addition, studies using basophil-deficient mice have revealed that basophils were responsible for cutaneous Th2 skewing to haptens and peptide antigens but not to protein antigens. Moreover, human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of skin diseases ranging from atopic dermatitis to autoimmune diseases. In this review, we will discuss the recent advances related to mast cells and basophils in human and murine cutaneous immune responses.

  6. Basophil-derived IL-6 regulates TH17 cell differentiation and CD4 T cell immunity

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    Yuk, Chae Min; Park, Hyeung Ju; Kwon, Bo-In; Lah, Sang Joon; Chang, Jun; Kim, Ji-Young; Lee, Kyung-Mi; Park, Su-Hyung; Hong, Seokchan; Lee, Seung-Hyo

    2017-01-01

    Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote TH17 cell differentiation. In the TH17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and TH17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of TH17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of TH17 cell differentiation, which is dependent on IL-6 secretion. PMID:28134325

  7. Role of human mast cells and basophils in bronchial asthma.

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    Marone, Gianni; Triggiani, Massimo; Genovese, Arturo; De Paulis, Amato

    2005-01-01

    Mast cells and basophils are the only cells expressing the tetrameric (alphabetagamma2) structure of the high affinity receptor for IgE (FcepsilonRI) and synthesizing histamine in humans. Human FcepsilonRI+ cells are conventionally considered primary effector cells of bronchial asthma. There is now compelling evidence that these cells differ immunologically, biochemically, and pharmacologically, which suggests that they might play distinct roles in the appearance and fluctuation of the asthma phenotype. Recent data have revealed the complexity of the involvement of human mast cells and basophils in asthma and have shed light on the control of recruitment and activation of these cells in different lung compartments. Preliminary evidence suggests that these cells might not always be detrimental in asthma but, under some circumstances, they might exert a protective effect by modulating certain aspects of innate and acquired immunity and allergic inflammation.

  8. Histamine content and secretion in basophils and mast cells.

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    Dvorak, A M

    1998-01-01

    Biochemical determinations of the histamine content and secretion from basophils and mast cells have been available for some time, and much of the complex anatomy of these cellular populations and their release reactions has been documented using the electron microscope. The ultrastructural analyses led to the description of vesicular transport between secretory granules and the plasma membrane as a mechanism for secretion from basophils and mast cells--a process termed piecemeal degranulation. Proof of concepts incorporated in a general degranulation model put forth in 1975 (DVORAK, H.F. and DVORAK, A.M.) requires high magnification imaging of a granule constituent in trafficking vesicles in the process of a stimulated release reaction in which the constituent release is monitored biochemically. Development and application of a new enzyme-affinity method to detect histamine at high magnifications in well-preserved ultrastructural samples have provided the necessary means to establish proof that appropriate secretagogues can stimulate the vesicular transport of histamine in basophils and mast cells during release reactions monitored biochemically. The background information necessary to the understanding of this result is presented here, as well as the development and verification of the diamine oxidase-gold method to image histamine in human mast cell granules as the test system. Also presented are applications using this technology to examine histamine stores and secretion in vitro, in vivo, and ex vivo in human basophils and mast cells and in mouse mast cells. Specifically examined are histamine stores developing in maturing mast cells induced to develop de novo from cultured human cord blood cells, secretagogue-stimulated release and recovery of histamine stores from isolated, purified human lung mast cells ex vivo, cytokine-stimulated degranulation of human skin mast cells and their histamine stores in vivo, piecemeal degranulation of human gut mast cells and

  9. Comparative electron microscopy of basophils and mast cells, in vivo and in vitro.

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    Eguchi, M

    1991-01-01

    We compared the fine structure and electron microscopic cytochemical findings of basophils and mast cells from humans, guinea pigs, rabbits, mice and rats. The particulate structure was the most frequently observed and most typical structure of human and rabbit basophil granules and of guinea pig mast cell granules. The most prominent feature of guinea pig basophils and murine mast cells was that the fine structure of the granules was homogeneous. The fine structure of the granules in guinea pig basophils resembled that in murine mast cells, while the fine structure of the granules of guinea pig mast cells resembled those in human and rabbit mast cells. In mouse mast cells in culture, the majority of the granules contained small vesicles, which were also observed in human basophils in culture and in mouse basophils in vivo. The degrees of cytochemical reactivity of acid mucopolysaccharides among the species were different. Peroxidase activity was positive in most basophils and in human mast cells. Among mammals, the granules of basophils and mast cells present heterogeneous fine structure. It is of interest that the basophil granules of some species resemble the mast cell granules rather than the basophil granules of other species.

  10. 89 Is Basophil Specific Response to Hymenoptera Venom Related to T Regulatory Cells?

    OpenAIRE

    Kucera, Petr; Hulikova, Katarina; Cvackova, Milada; Planska, Daniela; Riegerova, Kamila

    2012-01-01

    Background The exact mechanism of systemic hypersensitivity to venom is not exactly understood. It is suggested T cells with regulatory potential can downregulate other T cell subsets and effector cells, ex. mast cell or basophils. We focused on relationship of specific basophil reactivity in relationship to proportion of regulatory T cells. Methods Forty-five patients with history of systemic symptoms of allergy to Hymenoptera venom were included. Basophil reactivity before the treatment and...

  11. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

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    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type haematopoiesis. Interphase fluorescence in situ hybridisation (FISH) showed an 11q23 deletion. Given that the latency period between transplant and development of leukaemia was the longest reported to date, we discuss the mechanisms underlying delayed leukaemia onset. PMID:23675279

  12. The STAT5-GATA2 pathway is critical in basophil and mast cell differentiation and maintenance.

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    Li, Yapeng; Qi, Xiaopeng; Liu, Bing; Huang, Hua

    2015-05-01

    Transcription factor GATA binding protein 2 (GATA2) plays critical roles in hematopoietic stem cell survival and proliferation, granulocyte-monocyte progenitor differentiation, and basophil and mast cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation, but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells, as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.

  13. Difference in CD22 molecules in human B cells and basophils

    OpenAIRE

    Toba, Ken; Hanawa, Haruo; Fuse, Ichiro; Sakaue, Minori; Watanabe, Kenichi; Uesugi, Yumiko; Higuchi, Wataru; Takahashi, Wataru; Aizawa, Yoshifusa; 鳥羽, 健

    2002-01-01

    Objective. CD22 is believed to be restricted to normal and neoplastic B cells. Human basophils were found to express CD22 molecules. Among the antibodies against CD22, Leu14, which recognized the ligand binding domain reacted to basophils, and B3 and 4KB128, which recognized the amino terminus side and carboxy terminus side of the ligand binding epitope, respectively, did not. To clarify the difference of CD22 antigenicity in human B cells and basophils, we investigated RNA sequence and struc...

  14. Mutual interaction of Basophils and T cells in chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Marika eSarfati

    2015-08-01

    Full Text Available Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high affinity receptor for IgE (FcεR1, release histamine, inflammatory mediators and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid and non-lymphoid tissues and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2 and Th17 cells, as well as their potential role in IgE-independent non allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.

  15. A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Dissing, S; Skov, P S;

    2005-01-01

    Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation...

  16. Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4

    DEFF Research Database (Denmark)

    Jinquan, T; Jacobi, H H; Jing, C

    2000-01-01

    The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function...... of SDF-1alpha in basophils are unknown....

  17. Identification of novel Notch target genes in T cell leukaemia

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    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  18. Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

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    Ferran, M; Gallardo, F; Ferrer, A M; Salar, A; Pérez-Vila, E; Juanpere, N; Salgado, R; Espinet, B; Orfao, A; Florensa, L; Pujol, R M

    2008-05-01

    Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77-year-old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

  19. Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.

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    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-12-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.

  20. Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells

    DEFF Research Database (Denmark)

    Jensen, C; Svendsen, U G; Thastrup, Ole;

    1987-01-01

    The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic...... was reflected in the sensitivity of the cells to extracellular calcium, since inhibition of the release could be counteracted by increasing the extracellular concentration of calcium....

  1. Infiltration of hypertrophic esophageal smooth muscle by mast cells and basophils.

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    Tung, H N; Schulze-Delrieu, K; Shirazi, S

    1993-01-01

    Partial obstruction leads to chronic distension and muscular hypertrophy of the opossum esophagus. The smooth muscle cells of the circular muscle layer enlarge, become pleomorphic and are surrounded by an amorphous ground substance in the extracellular space. Here we describe the histological and ultrastructural features of a peculiar cellular infiltrate in the hypertrophic smooth muscle. The infiltrate consisted uniquely of mast cells and basophils. In per unit area, the number of mast cells increased from 0.9 +/- 0.1 cells in controls to 3.7 +/- 0.2 in hypertrophic smooth muscle; the corresponding numbers for basophils were 2.5 +/- 0.2 and 7.2 +/- 0.3 cells. Cells were seen primarily in the septal spaces of the circular muscle layer and at the interface of the circular and longitudinal muscle layer. The cytoplasm of basophils is normally packed with round and oval granules. The granules stain metachromatically and with varying intensity on Wright-Giemsa stains. On transmission electronmicroscopy, granules display a membrane and a great diversity in the structure of their luminal contents. In hypertrophic muscle, most granules were discharging their contents into the cytoplasm or extracellular space. The membranes of adjacent empty granules then fused to form a chain of vacuoles. Similar changes occurred also in the mast cells which differed from the basophil by their lack of nuclear lobulation and by the greater homogeneity of their cytoplasmic granules. It is possible that these inflammatory cells are involved in the reconstruction of the smooth muscle and its connective tissue which occur during esophageal distension and hypertrophy.

  2. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

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    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  3. Genetic analysis of basophil function in vivo

    OpenAIRE

    Sullivan, Brandon M.; Liang, Hong-Erh; Bando, Jennifer K.; Wu, Davina; Cheng, Laurence E.; McKerrow, James K.; Allen, Christopher D.C.; Locksley, Richard M.

    2011-01-01

    Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive IL-4 reporter alleles, we demonstrate that basophil IL-4 production occurs by a CD4+ T cell-dependent process restricted to affected peripheral tissues. We genetically marked and specifically deleted basophils and demonstrate that basophils do not mediate TH2 priming in vivo. Two-photon imaging confirmed that basophils do not interact with antigen-specific T cells in lymph nodes, but can ...

  4. Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells.

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    Patella, V; Casolaro, V; Björck, L; Marone, G

    1990-11-01

    Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in

  5. Monomeric immunoglobulin E stabilizes FcepsilonRIalpha from the human basophil cell line KU812 by protecting it from natural turnover

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Hansen, Jens Bo; Dissing, S;

    2003-01-01

    The high affinity IgE receptor (FcepsilonRI) on mast cells and basophils is up-regulated by its own ligand IgE; however, the mechanism is unknown.......The high affinity IgE receptor (FcepsilonRI) on mast cells and basophils is up-regulated by its own ligand IgE; however, the mechanism is unknown....

  6. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

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    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  7. Protein Fv produced during vital hepatitis is a novel activator of human basophils and mast cells.

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    Patella, V; Bouvet, J P; Marone, G

    1993-11-15

    Protein Fv is found in the normal liver and is released in the stools of patients suffering from viral hepatitis. Protein Fv isolated from five patients stimulated the release of histamine and sulfidopeptide leukotriene C4 from purified and unpurified peripheral blood basophils. Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion, whereas removal of putative contaminating Ig did not modify the releasing activity. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE). There was an excellent correlation (Spearman rank coefficient (rs) = 0.83; p ADZ) blocked both anti-IgE- and protein Fv-induced releases, whereas human polyclonal IgG and a monoclonal IgG purified from another myeloma patient (patient ZEG) selectively blocked protein Fv-induced secretion. Protein Fv also induced the release of preformed (histamine and tryptase) and de novo synthesized mediators (sulfidopeptide leukotriene C4 and/or PGD2) from mast cells purified from human lung parenchyma and skin tissues. There was a significant correlation between the maximal percent histamine release induced by protein Fv and anti-IgE from skin mast cells (rs = 0.63; p < 0.01). There was also an excellent correlation between histamine and tryptase release caused by protein Fv from both lung (rs = 0.80; p < 0.001) and skin mast cells (rs = 0.70; p < 0.01). Thus, we established that protein Fv acts as a novel activator of human basophils and mast cells presumably by interacting with the VH domain of the IgE.

  8. IL-33 induces IL-9 production in human CD4+ T cells and basophils

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Britta Cathrina; Jensen, Bettina M.

    2011-01-01

    IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral...

  9. Evaluation of Allergy Effector Cell Function: Suppression of Basophils in Chronic Helminth Infections

    Science.gov (United States)

    2011-01-01

    basophils are probably best known for their participation in the effector phase of immediate hypersensitivity reactions, some studies have suggested...had Schistosoma mansoni infections were then sensitized to Penicillin V. When mice in these groups were challenged with Pen V, body temperature was... hypersensitivity reactions, reduced basophil functionality could be one way helminth infection protects against allergic disease. 2. Determine the

  10. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation.

    Science.gov (United States)

    Park, Hyun Jung; Lee, Sung Won; Park, Se-Ho; Hong, Seokmann

    2016-01-01

    Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA) treatment suppresses the development of allergic diseases such as atopic dermatitis (AD). Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT) cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to the design and

  11. Genetic analysis of basophil function in vivo.

    Science.gov (United States)

    Sullivan, Brandon M; Liang, Hong-Erh; Bando, Jennifer K; Wu, Davina; Cheng, Laurence E; McKerrow, James K; Allen, Christopher D C; Locksley, Richard M

    2011-06-01

    Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive interleukin 4 (Il4) reporter alleles, we demonstrate here that basophil IL-4 production occurs by a CD4(+) T cell-dependent process restricted to the peripheral tissues affected. We genetically marked and achieved specific deletion of basophils and found that basophils did not mediate T helper type 2 (T(H)2) priming in vivo. Two-photon imaging confirmed that basophils did not interact with antigen-specific T cells in lymph nodes but engaged in prolonged serial interactions with T cells in lung tissues. Although targeted deletion of IL-4 and IL-13 in either CD4(+) T cells or basophils had a minimal effect on worm clearance, deletion from both lineages demonstrated a nonredundant role for basophil cytokines in primary helminth immunity.

  12. In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

    Science.gov (United States)

    Choi, J. W.; Shin, S. C.; Kim, S.; Chung, E. R.; Bang, J. H.; Cho, G. I.; Choi, S. D.; Park, Y. S.; Jang, T. S.; Yoo, Y. M.; Lee, S. S.; Hwang, D. G.

    2010-05-01

    In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequence of the cytokine genes, such as the tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.

  13. Basophil stimulation and signaling pathways.

    Science.gov (United States)

    Knol, Edward F; Gibbs, Bernhard F

    2014-01-01

    Despite growing use of flow cytometry to analyze the functional characteristics of primary basophils the intracellular signaling cascades that control their ability to elaborate various inflammatory mediators and cytokines remain comparatively obscure. Additionally, some studies require the analysis of pro-allergic and inflammatory mediators, such as histamine, LTC4, and various basophil-derived cytokines (e.g., IL-4 and IL-13). Elucidation of intracellular signaling proteins by Western blotting, cytosolic free calcium concentration by spectrofluorophotometry, and detection of mediator releases, as well as analysis of gene expressions by RT-PCR, generally require relatively large numbers of purified basophils. In selected assays, flow cytometry can enable the analysis of relatively low cell numbers and purity for the expression of intracellular signaling proteins or measurement of cytosolic free calcium concentrations by basophil-specific gating strategies. Unfortunately, many aspects of signal transduction relevant to human basophils cannot be readily extrapolated from the use of basophil or mast cell lines. This chapter therefore focuses on how to employ primary human basophils for studying mediator releases and signaling characteristics.

  14. Screening anaphylactic components of MaiLuoNing injection by using rat basophilic leukemia-2H3 cell membrane chromatography coupled with HPLC-ESI-TOF-MS.

    Science.gov (United States)

    Han, Shengli; Lv, Yanni; Xue, Wenjing; Cao, Jiao; Cui, Ronghua; Zhang, Tao

    2016-02-01

    MaiLuoNing injection is a traditional Chinese medicine that used clinically since the 1950s in China. However, anaphylactic reactions, through the potentiation of mast cell degranulation, have been reported. In the present study, a rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization-ion trap-time of flight-mass spectrometry method was established for screening, analyzing, and identifying the potential anaphylactic components of MaiLuoNing injection. Harpagoside, a potential degranulator of rat basophilic leukemia-2H3 cells, was retained in rat basophilic leukemia-2H3 cell membrane chromatography. We aimed to evaluate the retained components to determine which of those were capable of inducing degranulation of basophilic leukemia cells. A β-hexosaminidase assay revealed that harpagoside can induce rat basophilic leukemia-2H3 cell degranulation in a dose-dependent manner. BLBA/c mice also exhibit passive cutaneous anaphylaxis in response to harpagoside. These results indicate that rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization ion trap time-of-flight mass spectrometry is effective in screening for the anaphylactic components of MaiLuoNing injection.

  15. Membrane and cytoskeletal changes associated with IgE-mediated serotonin release from rat basophilic leukemia cells

    OpenAIRE

    1985-01-01

    Binding of antigen to IgE-receptor complexes on the surface of RBL-2H3 rat basophilic leukemia cells is the first event leading to the release of cellular serotonin, histamine, and other mediators of allergic, asthmatic, and inflammatory responses. We have used dinitrophenol- conjugated bovine serum albumin (DNP-BSA) as well as the fluorescent antigen, DNP-B-phycoerythrin, and the electron-dense antigen, DNP-BSA- gold, to investigate dynamic membrane and cytoskeletal events associated with th...

  16. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  17. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins

    OpenAIRE

    Jeanette Grundström; Jenny M Reimer; Sofia E Magnusson; Gunnar Nilsson; Sara Wernersson; Lars Hellman

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transc...

  18. CD27-triggering on primary plasma cell leukaemia cells has anti-apoptotic effects involving mitogen activated protein kinases

    NARCIS (Netherlands)

    Guikema, JEJ; Vellenga, E; Abdulahad, WH; Hovenga, S; Bos, NA

    2004-01-01

    Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was

  19. Biochemical and phenotypic characterization of human basophilic cells derived from dispersed fetal liver with murine T cell factors

    Energy Technology Data Exchange (ETDEWEB)

    Seldin, D.C.; Caulfield, J.P.; Hein, A.; Osathanondh, R.; Nabel, G.; Schlossman, S.F.; Stevens, R.L.; Austen, K.F.

    1986-03-15

    Metachromatically granulated cells were generated from human fetal liver stem cells cultured in heterologous mouse conditioned medium rich in interleukin 3. After 2 to 3 wk of culture with biweekly changes of medium and selection of nonadherent cells, all cells present in five cultures had cytoplasmic granules. Ultrastructurally, many granules contained fibrillar material or electron-dense cores with fibrils and vesicular fragments. In addition, the granules of many cells were filled with electron-dense material, which in some cases had a fine structure consisting of concentric whorls or a reticular pattern. Analysis of high-affinity IgE receptors on the cultured cells by flow cytometry demonstrated a unimodel fluorescence pattern, suggesting that most cells were in the basophil or mast cell lineage. The cells contained 52 ng/10/sup 6/ cells of histamine and incorporated (/sup 35/S)sulfate at an average rate of 31,300 cpm/10/sup 6/ cells/4 hr into 175,000 m.w. chondroitin sulfate A proteoglycans. Upon activation with 1 ..mu..M calcium ionophore A23187, the cultured cells released 53% of their cell-associated histamine and metabolized arachidonic acid to 15.0 ng/10/sup 6/ cells of immunoreactive leukotriene C/sub 4/ equivalents, 0.5 ng/10/sup 6/ cells of leukotriene B/sub 4/, and 3.1 ng/10/sup 6/ cells of prostaglandin D/sub 2/ (means, n = 3). Thus, stem cells present in human fetal liver give rise, as do stem cells in mouse fetal liver, to metachromatically granulated cells when cultured in the presence of mouse interleukin 3.

  20. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Van Vlierberghe, Pieter; Pieters, Rob; Beverloo, H Berna; Meijerink, Jules P P

    2008-10-01

    Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

  1. Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

    Science.gov (United States)

    Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

    2015-08-01

    Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Dopamine inhibits proliferation, induces differentiation and apoptosis of K562 leukaemia cells

    Institute of Scientific and Technical Information of China (English)

    HE Qun; YUAN Lin-bo

    2007-01-01

    Background Dopamine exerts its effects mainly in nervous system through D1, D2 or D3 receptors. There are few reports dealing with the effects of dopamine on leukaemia cells. However, some dopamine agonists or antagonists do show biological effects on some types of leukaemia cells. Here, we report the effects of dopamine on the proliferation,differentiation and apoptosis of K562 leukaemia cells.Methods Proliferation was determined by MTT assay and cell counting both in liquid and semisolid cultures.Differentiation was verified by morphology, benzidine staining and flow cytometry. Apoptosis was checked by Hoechst 33258 staining and flow cytometry. The two groups were untreated group and treated group (dopamine 10-9 mol/L-10-4mol/L).Results In liquid culture, MTT assay and colony assay, dopamine inhibited proliferation of K562 cells. Inhibition rate was 29.28% at 10-6 mol/L and 36.10% at 10-5 mol/L after culture for 5 days in MTT assay. In benzidine staining and CD71 expression, dopamine induced K562 cells toward erythroid differentiation by increased 155% at 10-6 mol/L and by 171% at 10-5 mol/L after culture for 5 days in benzidine staining. In Hoechst 33258 staining and flow cytometry,dopamine induced K562 cells toward apoptosis. The sub G1 peak stained by PI was 14.23% at 10-4 mol/L dopamine after culture for 3 days compared with the control (0.81%) in flow cytometry.Conclusion Dopamine inhibites proliferation and induces both differentiation and apoptosis of K562 leukaemia cells.

  3. Basophils and skin disorders.

    Science.gov (United States)

    Borriello, Francesco; Granata, Francescopaolo; Marone, Gianni

    2014-05-01

    Since their discovery in 1879, basophils have been viewed as circulating blood granulocytes with limited immune function. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for basophils in several skin disorders. Human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of diseases ranging from chronic idiopathic urticaria to systemic lupus erythematosus. In mouse models, basophils participate in IgE-mediated chronic allergic inflammation of the skin and have a protective role in tick infestation. In this review, we discuss critical advances in our understanding of basophil biology and their roles in the pathophysiology of skin disorders.

  4. Newly appreciated roles for basophils in allergy and protective immunity.

    Science.gov (United States)

    Karasuyama, H; Obata, K; Wada, T; Tsujimura, Y; Mukai, K

    2011-09-01

    Basophils are evolutionarily conserved in many animal species, in spite of the fact that they account for basophils have an indispensable and nonredundant role in vivo, even though they show some phenotypic similarity with tissue-resident mast cells. However, their functional significance remained uncertain long after Paul Ehrlich discovered them as blood-circulating cells with basophilic granules more than 130 years ago. The study of basophils has been far behind that of mast cells, owing to the rarity of basophils and the paucity of tools for their detection and functional analysis. Recent development of novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, has greatly advanced basophil research and illuminated previously unrecognized roles of basophils. We now appreciate that basophils and mast cells play distinct roles in immune responses. Basophils have crucial roles in the development of acute and chronic allergic responses, the protective immunity against ecto- and endoparasites, and the regulation of acquired immunity, including the augmentation of humoral memory responses and the initiation of Th2 responses. Thus, basophils are no longer the neglected minority and are key players in the immune system.

  5. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  6. Antiallergic tea catechin, (-)-epigallocatechin-3-O-(3-O-methyl)-gallate, suppresses FcepsilonRI expression in human basophilic KU812 cells.

    Science.gov (United States)

    Fujimura, Yoshinori; Tachibana, Hirofumi; Maeda-Yamamoto, Mari; Miyase, Toshio; Sano, Mitsuaki; Yamada, Koji

    2002-09-25

    We previously found that the O-methylated derivative of (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG' '3Me), has potent antiallergic activity. The high-affinity IgE receptor, FcepsilonRI, is found at high levels on basophils and mast cells and plays a key role in a series of acute and chronic human allergic reactions. To understand the mechanism of action for the antiallergic EGCG' '3Me, the effect of EGCG' '3Me on the cell surface expression of FcepsilonRI in human basophilic KU812 cells was examined. Flow cytometric analysis showed that EGCG' '3Me was able to decrease the cell surface expression of FcepsilonRI. Moreover, immunoblot analysis revealed that total cellular expression of the FcepsilonRI alpha chain decreased upon treatment with EGCG' '3Me. FcepsilonRI is a tetrameric structure comprising one alpha chain, one beta chain, and two gamma chains. The level of mRNA production of each subunit in KU812 cells was investigated. EGCG' '3Me reduced FcepsilonRI alpha and gamma mRNA levels. The cross-linkage of FcepsilonRI causes the activation of basophils, which leads to the secretion of inflammatory mediators including histamine. EGCG' '3Me treatment inhibited the FcepsilonRI cross-linking-induced histamine release. These results suggested that EGCG' '3Me can negatively regulate basophil activation through the suppression of FcepsilonRI expression.

  7. IgE in the absence of allergen induces the expression of monocyte chemoattractant protein-1 in the rat basophilic cell-line RBL-2H3.

    Science.gov (United States)

    Ahn, Ki Bum; Jeon, Jun Ho; Kang, Seok-Seong; Chung, Dae Kyun; Yun, Cheol-Heui; Han, Seung Hyun

    2014-11-01

    Recently, basophils have been suggested to produce inflammatory mediators in response to IgE in the absence of allergens. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the initiation of inflammatory responses by recruiting various immune cells to the site of allergic inflammation. In the present study, we examined whether IgE under allergen-free conditions could stimulate basophils and lead to the production of MCP-1. Exposure of the rat basophilic cell-line RBL-2H3 to IgE without allergen resulted in a dose- and time-dependent induction of MCP-1 expression at both the mRNA and protein level. Although allergen was not necessary for IgE-induced MCP-1 expression, it was essential for degranulation as determined by β-hexosaminidase release assay. IgE enhanced phosphorylation of MAP kinases including ERK, p38 kinase, and JNK. However, IgE-induced MCP-1 expression was attenuated by inhibitors for JNK and PKC. Concomitantly, IgE induced activation of AP-1, which is an important transcription factor for MCP-1 gene expression in RBL-2H3 cells. Taken together, our results suggest that IgE alone is sufficient to stimulate basophils to increase expression of MCP-1, which in turn might contribute to the inflammatory response.

  8. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    Science.gov (United States)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  9. Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Laura Zambonin

    2012-01-01

    Full Text Available Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL, whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach.

  10. Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Thastrup, Ole

    1987-01-01

    Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S...... with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane...... sialic acid in basophil leukocytes is involved in the regulation of histamine release, possibly by a modulation of the transmembraneous calcium fluxes preceding histamine release....

  11. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  12. Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E.

    Science.gov (United States)

    Pramod, S N; Venkatesh, Y P; Mahesh, P A

    2007-06-01

    A major factor in non-allergic food hypersensitivity could be the interaction of dietary lectins with mast cells and basophils. Because immunoglobulin E (IgE) contains 10-12% carbohydrates, lectins can activate and degranulate these cells by cross-linking the glycans of cell-bound IgE. The present objective focuses on the effect of potato lectin (Solanum tuberosum agglutinin; STA) for its ability to release histamine from basophils in vitro and mast cells in vivo from non-atopic and atopic subjects. In this study, subjects were selected randomly based on case history and skin prick test responses with food, pollen and house dust mite extracts. Skin prick test (SPT) was performed with STA at 100 microg/ml concentration. Histamine release was performed using leucocytes from non-atopic and atopic subjects and rat peritoneal exudate cells. SPT on 110 atopic subjects using STA showed 39 subjects positive (35%); however, none showed STA-specific IgE; among 20 non-atopic subjects, none were positive by SPT. Maximal histamine release was found to be 65% in atopic subjects (n = 7) compared to 28% in non-atopic subjects (n = 5); the release was inhibited specifically by oligomers of N-acetylglucosamine and correlates well with serum total IgE levels (R(2) = 0.923). Binding of STA to N-linked glycoproteins (horseradish peroxidase, avidin and IgG) was positive by dot blot and binding assay. As potato lectin activates and degranulates both mast cells and basophils by interacting with the chitobiose core of IgE glycans, higher intake of potato may increase the clinical symptoms as a result of non-allergic food hypersensitivity in atopic subjects.

  13. Mechanosensitive channel activity and F-actin organization in cholesterol-depleted human leukaemia cells.

    Science.gov (United States)

    Morachevskaya, Elena; Sudarikova, Anastasiya; Negulyaev, Yuri

    2007-04-01

    This study focuses on the functional role of cellular cholesterol in the regulation of mechanosensitive cation channels activated by stretch in human leukaemia K562 cells. The patch-clamp method was employed to examine the effect of methyl-beta-cyclodextrin (MbetaCD), a synthetic cholesterol-sequestering agent, on stretch-activated single currents. We found that cholesterol-depleting treatment with MbetaCD resulted in a suppression of the activity of mechanosensitive channels without a change in the unitary conductance. The probability that the channel was open significantly decreased after treatment with MbetaCD. Fluorescent microscopy revealed F-actin reorganization, possibly involving actin assembly, after incubation of the cells with MbetaCD. We suggest that suppression of mechanosensitive channel activation in cholesterol-depleted leukaemia cells is due to F-actin rearrangement, presumably induced by lipid raft destruction. Our observations are consistent with the notion that stretch-activated cation channels in eukaryotic cells are regulated by the membrane-cytoskeleton complex rather than by tension developed purely in the lipid bilayer.

  14. Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

    2015-02-01

    Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation.

  15. Selection of reference genes for quantitative PCR studies in purified B cells from B cell chronic lymphocytic leukaemia patients

    OpenAIRE

    Valceckiene, Vilma; Kontenyte, Rima; Jakubauskas, Arturas; Griskevicius, Laimonas

    2010-01-01

    Abstract Clinical heterogeneity of B-cell chronic lymphocytic leukaemia (B-CLL) makes it necessary to identify potent prognostic indicators to predict individual clinical course and select risk-adapted therapy. During the last years numerous gene expression models have been suggested as prognostic factors of B-CLL. Today quantitative polymerase chain reaction (qPCR) is a preferred method for rapid quantification of gene expression and validation of microarray data. Reliability of q...

  16. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.

    Directory of Open Access Journals (Sweden)

    Robert J Weeks

    Full Text Available Childhood acute lymphoblastic leukaemia (ALL is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity.Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5'-aza-2'-deoxycytidine (decitabine exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays.In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity.These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL.

  17. Human basophils express interleukin-4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Valent, P.; Besemer, J.; Kishi, K.; Di Padova, F.; Geissler, K.; Lechner, K.; Bettelheim, P. (Univ. of Vienna (Austria))

    1990-11-01

    Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed.

  18. Effects of bioactive compounds from carrots (Daucus carota L.), polyacetylenes, beta-carotene and lutein on human lymphoid leukaemia cells.

    Science.gov (United States)

    Zaini, Rana G; Brandt, Kirsten; Clench, Malcolm R; Le Maitre, Christine L

    2012-07-01

    New therapies for leukaemia are urgently needed. Carrots have been suggested as a potential treatment for leukaemia in traditional medicine and have previously been studied in other contexts as potential sources of anticancer agents. Indicating that carrots may contain bioactive compounds, which may show potential in leukaemia therapies. This study investigated the effects of five fractions from carrot juice extract (CJE) on human lymphoid leukaemia cell lines, together with five purified bioactive compounds found in Daucus carota L, including: three polyacetylenes (falcarinol, falcarindiol and falcarindiol-3-acetate) and two carotenoids (beta-carotene and lutein). Their effects on induction of apoptosis using Annexin V/PI and Caspase 3 activity assays analysed via flow cytometry and inhibition of cellular proliferation using Cell Titer Glo assay and cell cycle analysis were investigated. Treatment of all three lymphoid leukaemia cell lines with the fraction from carrot extracts which contained polyacetylenes and carotenoids was significantly more cytotoxic than the 4 other fractions. Treatments with purified polyacetylenes also induced apoptosis in a dose and time responsive manner. Moreover, falcarinol and falcarindiol-3-acetate isolated from Daucus carota L were more cytotoxic than falcarindiol. In contrast, the carotenoids showed no significant effect on either apoptosis or cell proliferation in any of the cells investigated. This suggests that polyacetylenes rather than beta-carotene or lutein are the bioactive components found in Daucus carota L and could be useful in the development of new leukemic therapies. Here, for the first time, the cytotoxic effects of polyacetylenes have been shown to be exerted via induction of apoptosis and arrest of cell cycle.

  19. A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia

    OpenAIRE

    Tempescul, Adrian; Feuerbach, Johanna; Ianotto, Jean-Christophe; Dalbies, Florence; Marion, Veronique; Bris, Marie-Josée; De Braekeleer, Marc; Berthou, Christian

    2008-01-01

    A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia phone: +33-298-223504 (Tempescul, Adrian) (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 29609 - Brest - FRANCE (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 2...

  20. Targeting Mast Cells and Basophils with Anti-FcεRIα Fab-Conjugated Celastrol-Loaded Micelles Suppresses Allergic Inflammation.

    Science.gov (United States)

    Peng, Xia; Wang, Juan; Li, Xianyang; Lin, Lihui; Xie, Guogang; Cui, Zelin; Li, Jia; Wang, Yuping; Li, Li

    2015-12-01

    Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FcεRIα Fab-conjugated celastrol-loaded micelles toward FcεRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FcεRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FcεRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FcεRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FcεRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FcεRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FcεRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FcεRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

  1. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Directory of Open Access Journals (Sweden)

    Jeanette Grundström

    Full Text Available Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95% and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP, charcot leyden crystal (CLC, eosinophil cationic protein (ECP, eosinophil derived neurotoxin (EDN and eosinophil peroxidase (EPO. Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that

  2. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Science.gov (United States)

    Grundström, Jeanette; Reimer, Jenny M; Magnusson, Sofia E; Nilsson, Gunnar; Wernersson, Sara; Hellman, Lars

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL)-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95%) and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP), charcot leyden crystal (CLC), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO). Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that eosinophils and

  3. Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors

    DEFF Research Database (Denmark)

    Poulsen, L K; Stahl Skov, P; Mosbech, H

    1988-01-01

    Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leucocytes from normal individuals. At first, the system was optimized with regard...

  4. Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation.

    Science.gov (United States)

    Rosa-Calatrava, Manuel; Puvion-Dutilleul, Francine; Lutz, Pierre; Dreyer, Dominique; de Thé, Hugues; Chatton, Bruno; Kedinger, Claude

    2003-10-01

    The product of adenovirus type 5 (Ad5) gene IX, protein IX (pIX), is a multifunctional protein that stabilizes the viral capsid and has transcriptional activity. We show that pIX also contributes to the Ad5-induced reorganization of the host-cell nuclear ultrastructure: pIX induces the formation of specific and dynamic nuclear inclusions, and the host promyelocytic leukaemia (PML) protein, which is the main structural organizer of PML bodies, is stably relocated and confined within the pIX-induced inclusions late in infection. Our results suggest that Ad5 has evolved a unique strategy that leads to the sustained neutralization of PML bodies throughout infection, thereby ensuring optimal viral proliferation.

  5. GATA-1 regulates the generation and function of basophils.

    Science.gov (United States)

    Nei, Yuichiro; Obata-Ninomiya, Kazushige; Tsutsui, Hidemitsu; Ishiwata, Kenji; Miyasaka, Masayuki; Matsumoto, Kenji; Nakae, Susumu; Kanuka, Hirotaka; Inase, Naohiko; Karasuyama, Hajime

    2013-11-12

    Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remains elusive. Here we show that basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.

  6. [Cytotoxicity of polyphenolic/flavonoid compounds in a leukaemia cell culture].

    Science.gov (United States)

    Josipović, Pavle; Orsolić, Nada

    2008-12-01

    Flavonoid components of propolis are biologically active substances with antioxidative, immunostimulative, immunomodulative, and anti-inflamatory properties. The aim of the study was to investigate their cytotoxic effect on different leukaemia cell lines. For this purpose we used five different flavonoids (quercetin, caffeic acid, chrysin, naringenin, and naringin) and five types of leukemia cell lines (MOLT, JURKAT, HL-60, RAJI and U937). Cells were cultured at 37 degrees C in the RPMI-1640 medium supplemented with 10% FCS in humified atmosphere with 5% of CO2. Flavonoids were added in the following concentrations: 100 microg mL(-1), 50 microg mL(-1), 25 microg mL(-1), or 12.5 microg mL(-1). The results show different dose- and cell-type-dependent cytotoxicity. Among the flavonoids, quercetin showed the strongest cytotoxic effect in all cell lines. Caffeic acid and chrisyn also expressed a high level of cytotoxicty. Treatment of U937 and HL-60 cell lines with low concentrations of chrisyn or naringenin stimulated cell proliferation. These results suggest a biphase effect of the tested compounds on monocyte cell lines. Cytotoxicity and growth stimulation mechanisms caused directly by flavonoids should further be investigated on the molecular level.

  7. A human monoclonal IgE antibody that binds to MGL_1304, a major allergen in human sweat, without activation of mast cells and basophils.

    Science.gov (United States)

    Ishii, Kaori; Hiragun, Makiko; Hiragun, Takaaki; Kan, Takanobu; Kawaguchi, Tomoko; Yanase, Yuhki; Tanaka, Akio; Takahagi, Shunsuke; Hide, Michihiro

    MGL_1304, a major allergen in human sweat for patients with atopic dermatitis and/or cholinergic urticaria, is secreted from Malassezia globosa on human skin. The amounts of MGL_1304 and IgE against MGL_1304 are evaluated by the histamine release test using basophils or mast cells sensitized with serum containing IgE against MGL_1304, and enzyme linked sorbent assay (ELISA) using MGL_1304 and anti-MGL_1304 antibodies. Here, we identified a human monoclonal IgE (ABS-IgE) that binds to the high affinity IgE receptor (FcεRI) and MGL_1304 with high affinity (KD = 1.99 nM) but does not release histamine from basophils and mast cells. An ELISA using ABS-IgE as a standard IgE revealed that the amount of IgE against MGL_1304 (1000 U/ml) in the standard sera of patients with AD, employed in our previous report, is 32 ng/ml. A sandwich ELISA using ABS-IgE as a detection antibody showed approximately 10 times lower detection limit for MGL_1304 than ELISA in which MGL_1304 is directly bound to an ELISA plate. Moreover, ABS-IgE prevented histamine release from mast cells and basophils by neutralizing MGL_1304 not only in a free form in solution, but also on FcεRI expressed on the cell surface without cell activation. ABS-IgE may be used both to quantify the amount of MGL_1304 and anti-MGL_1304 IgE, and possibly for the treatment of diseases caused/aggravated by type I allergy to MGL_1304.

  8. Orientation de la réponse immune par les basophiles

    OpenAIRE

    Galeotti, C.; Stephen-Victor, E.; Sharma, M; Kaveri, S.V.; Bayry, J.

    2016-01-01

    International audience; Basophils are infrequent granulocytes which are important for Th2 responses, protection against helminthic parasites and the pathogenesis of allergy and other inflammatory conditions. Recent reports suggest that in mice basophils function as antigen-presenting cells for mediation of Th2 responses. However, human basophils lack features of antigen-presenting cells.; Les basophiles sont de rares granulocytes et ont un rôle important dans les réponses Th2, dans la protect...

  9. Childhood T-cell acute lymphoblastic leukaemia expressing "Ia-like" antigen:" a case report.

    Science.gov (United States)

    Kupa, A; Beckman, I G; Bradley, J; Moore, H; Thomas, M; Zola, H; Cheney, K; Rice, M; Toogood, I

    1982-01-01

    A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.

  10. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    Science.gov (United States)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  11. Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes.

    Science.gov (United States)

    Hibi, T; Hirashima, N; Nakanishi, M

    2000-04-29

    In neuronal cells, it is generally agreed that SNARE proteins underlie the release of neurotransmitter. It is controversial, however, whether they also work functionally in the degranulation of RBL-2H3 cells because the expression of SNARE proteins has not been confirmed and the degranulation is not inhibited by tetanus toxin which cleaves one of SNARE proteins, VAMP-2. We investigated the expression and the localization of SNARE proteins including VAMP-7 which is insensitive to tetanus toxin. RT-PCR analysis showed the existence of SNARE proteins, including syntaxin-2, -3, -4, SNAP-23, VAMP-2, and VAMP-7. Experiments using GFP-conjugated proteins revealed that VAMP-7 was localized only in granule membranes, whereas syntaxin-3 was in both the plasma and granule membranes. Upon antigen stimulation, these proteins in granule membranes moved to the cell surface due to the fusion of granules with the plasma membrane. The results suggest the involvement of SNARE proteins in the degranulation of RBL-2H3 cells.

  12. Distinct morphophenotypic features of chronic B-cell leukaemias identified with CD1c and CD23 antibodies.

    Science.gov (United States)

    Orazi, A; Cattoretti, G; Polli, N; Delia, D; Rilke, F

    1991-07-01

    Morphological criteria usually applied to diagnose various subtypes of B-cell chronic lymphoid leukaemia are largely subjective. Immunophenotyping of 61 relevant cases using a selected panel of monoclonal antibodies (mAb), showed that CD1c and CD23 mAb were able to separate B-cell chronic lymphocytic leukaemia (B-CLL) from other chronic B-cell lymphoproliferative diseases. Lymphocytes of B-CLL were CD1c-, CD23+, whereas those of other types of chronic B-cell leukaemia were CD1c+/-, CD23-, and CD38/-. Non-B-CLL cases had a significantly higher amount of large peroxidase-negative (unstained) cells analyzed with an automated blood cell counter (Technicon H6000). This type of volumetric assessment allowed a separation between typical and "atypical" B-CLL, which otherwise were both CD1c-, and CD23+. These combinations of phenotypic markers corresponded to well-defined haematopathologic entities, conventionally diagnosed on peripheral blood (PB) and bone marrow smears, and on histologic sections of lymph nodes and spleen.

  13. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  14. CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF

    Directory of Open Access Journals (Sweden)

    Mayer Eric J

    2009-02-01

    Full Text Available Abstract Background CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF, sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres. Methods Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS CD133+ retinal cells were enriched from post mortem adult human retina. CD133+ retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation. Results We demonstrated purification (to 95% of CD133+ cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133+ retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133+ retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal. Conclusion These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.

  15. Effect of horse gram lectin (Dolichos biflorus agglutinin) on degranulation of mast cells and basophils of atopic subjects: identification as an allergen.

    Science.gov (United States)

    Pramod, Siddanakoppalu N; Krishnakantha, Thirumalai P; Venkatesh, Yeldur P

    2006-11-01

    Horse gram (Dolichos biflorus) is widely consumed in the tropical south Asian countries including rural areas of India. Since D. biflorus agglutinin (DBA) is an important dietary lectin in horse gram, we have studied its effect on the degranulation of mast cells and basophils of atopic subjects. Allergy to horse gram lectin has not been reported so far. Skin prick test (SPT) was performed with 100 microg/mL of DBA. DBA-specific IgE was detected by dot-blot, and ELISA. Histamine release (HR) assay was carried out using leukocytes from non-atopic and atopic subjects, and rat peritoneal exudate cells. Among the atopic group, 10 of 48 subjects (21%) were found to be positive for DBA by SPT, and none were positive in the non-atopic group (n=20). Two subjects out of the ten who tested positive for DBA by SPT were found to be sensitized to DBA as revealed by the presence of specific IgE by ELISA and dot-blot. The HR was found to be 2- to 3-fold higher in DBA-allergic subjects than in non-atopic and atopic subjects. Basophil HR by DBA was found to be similar in both non-atopic and atopic subjects. However, DBA induces activation of mast cells in vivo in a sub-population (21%) of atopic subjects. Two subjects have been identified as having food allergy to horse gram based on the presence of DBA-specific IgE with a positive correlation to basophil HR. This is the first report of food allergy to horse gram, and DBA has been identified as an allergen.

  16. A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells.

    Science.gov (United States)

    Medves, Sandrine; Auchter, Morgan; Chambeau, Laetitia; Gazzo, Sophie; Poncet, Delphine; Grangier, Blandine; Verney, Aurélie; Moussay, Etienne; Ammerlaan, Wim; Brisou, Gabriel; Morjani, Hamid; Géli, Vincent; Palissot, Valérie; Berchem, Guy; Salles, Gilles; Wenner, Thomas

    2016-07-01

    Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B-CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C-circle concentration, an extra-chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T-SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C-circle were evidenced. Nevertheless, compared with normal B cells, B-CLL cells showed an increase in T-SCE rate that was correlated with a strong down-regulation of the topoisomerase III alpha (TOP3A) expression, involved in the dissolution of Holliday Junctions (HJ), together with an increased expression of SLX1A, SLX4, MUS81 and GEN1, involved in the resolution of HJ. Altogether, our results suggest that the telomere maintenance mechanism of B-CLL cells do not preferentially use telomerase or ALT. Rather, the rupture of the dissolvasome/resolvasome balance may increase telomere shuffling that could homogenize telomere length, slowing telomere erosion in this disease.

  17. Identification and quantification of basophils in the airways of asthmatics following segmental allergen challenge.

    Science.gov (United States)

    Dijkstra, Dorothea; Hennig, Christian; Hansen, Gesine; Biller, Heike; Krug, Norbert; Hohlfeld, Jens M

    2014-07-01

    During asthma attacks, allergens activate sensitized basophils in the lung, thereby aggravating symptoms. Due to the paucity of basophils in bronchial lavage fluid and the lack of specific basophil detection and quantification methods, basophil-directed research in these samples was hampered in the past. This study aimed to establish and validate a flow cytometry-based basophil detection and quantification method for human basophils from bronchoalveolar lavage (BAL) and blood as a prerequisite for a better understanding of their pathogenic contribution and subtyping of asthma phenotypes. BAL and blood leukocytes from seasonal asthmatics were analyzed by flow cytometry. Chipcytometry, a highly sensitive single-cell analysis method, was used to validate the staining panel for basophils. Cell differentials of May-Grünwald-Giemsa-stained cytospins were used to compare basophil percentages. BAL basophils are identifiable as CD123(+) HLA-DR(-) CD3(-) CD14(-) CD19(-) CD20(-) CD56(-) cells in flow cytometrical analysis. Their identity was validated by Chipcytometry. CD203c was highly expressed by BAL basophils, whereas it was expressed at variable levels on blood basophils. The two quantification methods correlated, although more basophils were detected by flow cytometry. Furthermore, the increase in basophil percentages in the lung correlated with the decrease in the basophil percentages in the blood after allergen challenge. We here validated a reliable basophil quantification method, which is independent of the cell's activation and degranulation state. The results obtained with this method indicate that basophils are directly recruited from the blood circulation to the airway lumen.

  18. CD19-Chimeric Antigen Receptor T Cells for Treatment of Chronic Lymphocytic Leukaemia and Acute Lymphoblastic Leukaemia

    DEFF Research Database (Denmark)

    Lorentzen, C L; thor Straten, Per

    2015-01-01

    Adoptive cell therapy (ACT) for cancer represents a promising new treatment modality. ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting......-associated toxicities, which needs attention. Herein we review current data and discuss key aspects of this powerful approach to treat and potentially cure B cell malignancies....

  19. Nonreceptor protein tyrosine and lipid phosphatases in type I fc(epsilon) receptor-mediated activation of mast cells and basophils.

    Science.gov (United States)

    Heneberg, Petr; Dráber, Petr

    2002-08-01

    Protein tyrosine and lipid phosphorylations are early and critical events in type 1 Fc(epsilon) receptor (Fc(epsilon)RI)-mediated activation of mast cells and basophils. Tyrosine phosphorylation of Fc(epsilon)RI subunits as well as other signal transduction molecules reflects the balance between the action of protein tyrosine kinases and phosphatases. Similarly, the phosphate content of inositol phospholipids, involved in the recruitment of signalling molecules to the plasma membrane and the generation of secondary messengers, is the net result of the opposing effects of phosphoinositide kinases and lipid phosphatases. This review summarizes the current understanding of the structural and functional aspects of nonreceptor protein tyrosine phosphatases (SHP-1, SHP-2, HePTP, PTP20, PRL1, PRL2, PTP-MEG1 and PTP-MEG2) and lipid phosphatases (SHIP and SHIP2) in the activation of mast cells and basophils after Fc(epsilon)RI aggregation. New approaches towards a deeper understanding of the role of phosphatases in mast cell physiology are also discussed.

  20. Basophil leucocyte response in leprosy with lepromin-A

    Directory of Open Access Journals (Sweden)

    Okhandiar R

    1993-01-01

    Full Text Available Study of ′Basophil Leucocyte Response′ in two polar groups of leprosy patients (tuberculoid and lepromatous was undertaken employing Lepromin-A (Armadillo by the method of Open Window Technique of Rebuck. Significant infiltration of Basophils at the test side is demonstrated both at 48 hours and at 72 hours in lepromatous leprosy as compared to the control groups i.e., in placebo and tuberculin positive healthy volunteers as well as against tuberculoid leprosy group (p value being less than 0.05 and 0.001. The basophils also go into degeneration and degranulation at 72 hours. . The role of basophils in the different types of allergic reactions is discussed in context of above finding. The possible effect of high infiltration of basophils in lepromatous leprosy with its subsequent release of histamine and other factors by degranulation, and its possible role in immuno-regulation through specialised suppressor cells is postulated in the light of available data.

  1. Effects of oxatomide and derivatives on high affinity IgE receptor-activated signal transduction pathways in rat basophilic leukemia cells : Role of protein tyrosine hyperphosphorylation and inhibition of extracellular calcium influx

    NARCIS (Netherlands)

    Paulussen, JJC; Fischer, MJE; Roozendaal, RL; van der Heijden, VC; van Dijken, P.; de Mol, NJ; Janssen, LHM

    1998-01-01

    The antiallergic drug oxatomide and analogs inhibit mediator release from a rat basophilic leukemia (RBL-2H3) cell line, which is frequently used as a mast cell model. By investigating a series of derivatives of oxatomide with different inhibiting activities on exocytosis, we aimed to evaluate the r

  2. Phenotypically Dormant and Immature Leukaemia Cells Display Increased Ribosomal Protein S6 Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Monica Pallis

    Full Text Available Mechanistic/mammalian target of rapamycin (mTOR activity drives a number of key metabolic processes including growth and protein synthesis. Inhibition of the mTOR pathway promotes cellular dormancy. Since cells from patients with acute myeloid leukaemia (AML can be phenotypically dormant (quiescent, we examined biomarkers of their mTOR pathway activity concurrently with Ki-67 and CD71 (indicators of cycling cells by quantitative flow cytometry. Using antibodies to phosphorylated epitopes of mTOR (S2448 and its downstream targets ribosomal protein S6 (rpS6, S235/236 and 4E-BP1 (T36/45, we documented that these phosphorylations were negligible in lymphocytes, but evident in dormant as well as proliferating subsets of both mobilised normal stem cell harvest CD34+ cells and AML blasts. Although mTOR phosphorylation in AML blasts was lower than that of the normal CD34+ cells, p-4E-BP1 was 2.6-fold higher and p-rpS6 was 22-fold higher. Moreover, in contrast to 4E-BP1, rpS6 phosphorylation was higher in dormant than proliferating AML blasts, and was also higher in the immature CD34+CD38- blast subset. Data from the Cancer Genome Atlas show that rpS6 expression is associated with that of respiratory chain enzymes in AML. We conclude that phenotypic quiescence markers do not necessarily predict metabolic dormancy and that elevated rpS6 ser235/236 phosphorylation is characteristic of AML.

  3. A role for paclitaxel in the combination chemotherapy of acute myeloblastic leukaemia: preclinical cell culture studies.

    Science.gov (United States)

    Curtis, J E; Minkin, S; Minden, M D; McCulloch, E A

    1996-11-01

    Paclitaxel dose responses in culture have been investigated alone and in association with cytosine arabinoside (ARA-C) and all-trans retinoic acid (ATRA), with the objective of identifying a role for paclitaxel in the treatment of acute myeloblastic leukaemia (AML). Initial studies were done to determine if paclitaxel dose responses of AML blast cell precursors were altered by regulatory compounds known to modify the dose responses of ARA-C. In contrast to ARA-C, paclitaxel dose responses were independent of cell culture method, the growth factors G-CSF and GM-CSF, and the ligands all-trans retinoic acid (ATRA) and hydrocortisone. Most blast cell populations were sensitive to paclitaxel; compared with normal marrow progenitors the dose responses were markedly heterogenous with some more, and others less, sensitive. Remission marrow progenitor paclitaxel responses resembled those of AML blasts in heterogeneity. The cell culture model tested the effect of pacliataxel and ATRA on the ARA-C dose responses of OCI/ AML-5; paclitaxel exposure was either before or after ARA-C to test for an effect of schedule; ATRA was added to the MEC cultures after paclitaxel and ARA-C. Repeat experiments were done to test three dose levels each of paclitaxel and ATRA. When paclitaxel was given after ARA-C, synergism was found for all but one of the dose combinations tested; only three examples of synergy were seen when paclitaxel preceded ARA-C. The studies justify trials combining ARA-C, paclitaxel and ATRA using a schedule suggested by the cell culture findings.

  4. Lichen planus-like lesions as the first manifestation of adult T-cell leukaemia/lymphoma.

    Science.gov (United States)

    Sumida, Hayakazu; Sugaya, Makoto; Kamata, Masahiro; Suga, Hiraku; Miyagaki, Tomomitsu; Ohmatsu, Hanako; Fujita, Hideki; Sato, Shinichi

    2013-07-06

    Cutaneous involvement is frequent in adult T-cell leukaemia/lymphoma (ATLL), a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus type I (HTLV-I). Patients with ATLL manifest different types of skin lesions, including nodules, plaques, ulcers, erythroderma and purpura. It has been reported that this type of skin eruption is an independent prognostic factor for ATLL. We report here a rare case of a 62-year-old Japanese woman with smouldering-type ATLL, first manifested by lichen planus-like skin lesions on the lower leg. This case report highlights the multiplicity of skin manifestations in ATLL.

  5. Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-11-01

    Full Text Available The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS. More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1, heat shock 70 kDa protein 9 (HSPA9 and pyruvate kinase M2 (PKM2, were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

  6. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

    Science.gov (United States)

    Khajavinia, Amir; Varshosaz, Jaleh; Jafarian Dehkordi, Abbas

    2012-10-01

    The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide.

  7. CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

    Science.gov (United States)

    Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

    2016-04-01

    Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.

  8. Oral manifestations of acute leukaemia

    Directory of Open Access Journals (Sweden)

    Ivanović Mirjana

    2011-01-01

    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  9. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma.

    Directory of Open Access Journals (Sweden)

    Monique F M A Smeets

    Full Text Available The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL. Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways.

  10. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  11. Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

    DEFF Research Database (Denmark)

    Chen, Li; Ma, Shiliang; Li, Bo;

    2003-01-01

    Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101...... was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter...... in a transient transfection assay. A series of deletion and mutation analyses of the ETR101 gene promoter indicated that a 35 bp region immediately upstream of the TATA-box sequence, which contains a consensus cAMP response element (CRE) and a G+C-rich sequence, is the critical responsive element for Tax...

  12. Signaling transduction pathways involved in basophil adhesion and histamine release

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 andβ2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK)1/2 in basophil adhesion and histamine release (HR). Methods Basophils (purity of 10%-50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay.Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50 μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 μmol/L, 5 μmol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient.Conclusions Basophil spontaneous adhesion to Fn is mediated by β1-integrins whereas cytokine induced adhesion

  13. In vitro effects of extract of Senna alata (Ceasalpiniaceae on the polyamines produced by Leukaemia cells (L1210

    Directory of Open Access Journals (Sweden)

    C A Pieme

    2009-01-01

    Full Text Available The present study reports the effects of S. alata (Ceasalpiniaceae extract on the metabolism of polyamines resulting from the proliferation of leukaemia cells (L1210. The results established that the inhibition of cell proliferation was significantly increased with the concentration of extract from 28 to 32.80 % after 72 h. The percentage of cells viability changed significantly from 9.72 to 80 % when cells are treated with extract alone, in combination with DEMO or putrescine. The levels of the intracellular yield of putrescine, spermidine and spermine were also reduced by the extract compared to the control. The DEMO-extract complex enhanced the inhibition of the production polyamines up to 95 %. In opposite, the complex S. alata- putrescine complex stimulated significantly its biosynthesis of polyamines. A significant reduction of the level of protein after 72 h of treatment was observed. This result corroborated with the reduction of polyamines resulting from inhibition cell proliferation.

  14. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...... in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  15. Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells.

    Science.gov (United States)

    Chen, Ying-Jung; Wang, Jeh-Jeng; Chang, Long-Sen

    2011-11-01

    1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells.

  16. An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor.

    Science.gov (United States)

    Suzukawa, Maho; Iikura, Motoyasu; Koketsu, Rikiya; Nagase, Hiroyuki; Tamura, Chise; Komiya, Akiko; Nakae, Susumu; Matsushima, Kouji; Ohta, Ken; Yamamoto, Kazuhiko; Yamaguchi, Masao

    2008-11-01

    Basophils are thought to play pivotal roles in allergic inflammation through rapid release of chemical mediators in addition to sustained production of Th2 cytokines, including IL-4. A newly identified cytokine, IL-33, has been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. The present study was conducted to elucidate whether IL-33 acts directly on, and affects the functions of, human basophils. Real-time PCR analysis showed that basophils express transcripts for ST2. The expression levels were significantly higher compared with eosinophils and neutrophils, and treatment with IL-33 significantly up-regulated basophil ST2 mRNA expression. Expressions of IL-4 and IL-13 mRNA were also up-regulated by IL-33, and there was also enhanced secretion of IL-4 protein. IL-33 increased the surface levels of basophil CD11b expression and enhanced basophil adhesiveness. Although IL-33 failed to directly induce degranulation or attract basophils, it exerted priming effects on basophils. It enhanced degranulation in response to IgE-crosslinking stimulus and also enhanced basophil migration toward eotaxin without changing surface CCR3. Also, IL-33 synergistically enhanced IL-4 production and CD11b expression by IL-3-stimulated basophils. Neutralization using Ab specific for ST2 significantly diminished the enhancing effects of IL-33 on both basophil CD11b expression and migration toward eotaxin, indicating that IL-33 signals via ST2 expressed on basophils. This study revealed that IL-33 potently regulates migration and activation of human basophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant inflammation by acting not only on lymphocytes but also on effector cells such as basophils.

  17. Multipronged functional proteomics approaches for global identification of altered cell signalling pathways in B-cell chronic lymphocytic leukaemia.

    Science.gov (United States)

    Díez, Paula; Lorenzo, Seila; Dégano, Rosa M; Ibarrola, Nieves; González-González, María; Nieto, Wendy; Almeida, Julia; González, Marcos; Orfao, Alberto; Fuentes, Manuel

    2016-04-01

    Chronic lymphocytic leukaemia (CLL) is a malignant B cell disorder characterized by its high heterogeneity. Although genomic alterations have been broadly reported, protein studies are still in their early stages. Herein, a 224-antibody microarray has been employed to study the intracellular signalling pathways in a cohort of 14 newly diagnosed B-CLL patients as a preliminary study for further investigations. Several protein profiles were differentially identified across the cytogenetic and molecular alterations presented in the samples (deletion 13q14 and 17p13.1, trisomy 12, and NOTCH1 mutations) by a combination of affinity and MS/MS proteomics approaches. Among others altered cell signalling pathways, PKC family members were identified as down-regulated in nearly 75% of the samples tested with the antibody arrays. This might explain the rapid progression of the disease when showing p53, Rb1, or NOTCH1 mutations due to PKC-proteins family plays a critical role favouring the slowly progressive indolent behaviour of CLL. Additionally, the antibody microarray results were validated by a LC-MS/MS quantification strategy and compared to a transcriptomic CLL database. In summary, this research displays the usefulness of proteomic strategies to globally evaluate the protein alterations in CLL cells and select the possible biomarkers to be further studied with larger sample sizes.

  18. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: biological background and prognostic impact. Results from the NOPHO ALL-92 and ALL-2000 studies

    DEFF Research Database (Denmark)

    Vaitkeviciene, G; Forestier, E; Hellebostad, M;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1–15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  19. Eosinophilic leukaemia in a cat.

    Science.gov (United States)

    Sharifi, Hassan; Nassiri, Seyed Mahdi; Esmaelli, Hossein; Khoshnegah, Javad

    2007-12-01

    A 14-year-old female domestic shorthair cat was presented to Tehran University Veterinary Teaching Hospital for a persistent fever, anorexia, intermittent vomiting, weight loss and weakness. The main clinical signs were pale mucous membranes, dehydration and splenomegaly. The complete blood count and serum biochemistry tests revealed non-regenerative anaemia, thrombocytopenia and increased alkaline phosphatase (ALP) activity. An enzyme-linked immunosorbent assay (ELISA) test for feline leukaemia virus was negative. Blood film and bone marrow examination revealed a large number of immature eosinophils with variable sizes and numbers of faintly azurophilic granules. Cytochemical staining of blood film demonstrated 70% positive cells for ALP activity. Four percent CD34 positive cells were detected by flow cytometry. As eosinophilic leukaemia is difficult to identify by light microscopy, well-defined diagnostic criteria and the use of flow cytometry and cytochemical staining can improve the ability to correctly diagnose this type of leukaemia in cats.

  20. Analysis of allergens in tubeimu saponin extracts by using rat basophilic leukemia 2H3 cell-based affinity chromatography coupled to liquid chromatography and mass spectrometry.

    Science.gov (United States)

    Zhang, Tao; Han, Shengli; Liu, Qi; Guo, Ying; He, Langchong

    2014-11-01

    An affinity two-dimensional chromatography method was developed for the recognition, separation, and identification of allergic components from tubeimu saponin extracts, a preparation often injected to treat various conditions as indicated by traditional Chinese medicine. Rat basophilic leukemia-2H3 cell membranes were used as the stationary phase of a membrane affinity chromatography column to capture components with affinity for mast cells that could be involved in a degranulation reaction. The retained components were enriched and analyzed by membrane affinity chromatography with liquid chromatography and mass spectrometry via a port switch valve. Suitability and reliability of the method was investigated using appropriate standards, and then, the method was applied to identify components retained from tubeimu saponin extracts. Tubeimoside A was identified in this way as a potential allergen, and degranulation assays confirmed that tubeimoside A induces RBL-2H3 cell degranulation in a dose-dependent manner. An increase in Ca(2+) influx indicated that degranulation induced by tubeimoside A is likely Ca(2+) dependent. Coupled with the degranulation assay, RBL-2H3 cell-based affinity chromatography coupled with liquid chromatography and mass spectrometry is an effective method for screening and identifying allergic components from tubeimu saponin extracts.

  1. Genotoxicity of alkene epoxides in human peripheral blood mononuclear cells and HL60 leukaemia cells evaluated with the comet assay.

    Science.gov (United States)

    Fabiani, Roberto; Rosignoli, Patrizia; De Bartolomeo, Angelo; Fuccelli, Raffaela; Morozzi, Guido

    2012-08-30

    Volatile organic compounds (VOCs) exert their carcinogenic activity through the production of epoxide metabolites. Because of their high reactivity some epoxides are also produced in the chemical industry for the synthesis of other compounds. Therefore, human exposure to VOCs epoxides does occur and may be an important human health concern. In this study, the in vitro genotoxic potential of epoxides originating from 1,3-butadiene (3,4-epoxy-1-butene: EB; 1,2:3,4-diepoxybutane: DEB), isoprene (3,4-epoxy-2-methyl-1-butene: IO), styrene (styrene-7,8-oxide: SO), propylene (propylene oxide: PO) and 1-butene (1,2-epoxy-butane: BO) in human peripheral blood mononuclear cells (PBMCs) and promyelocytic leukaemia cells (HL60) was measured with the comet assay (single-cell gel electrophoresis, SCGE). The effect of inclusion of foetal calf serum (FCS, 5%) in the cell-culture medium and different durations of exposure (2h, 24h) were also investigated. All epoxides tested produced DNA damage in a concentration range that did not reduce cell viability. HL60 cells were more resistant than PBMCs to the DNA damage induced by the different epoxides. With the exception of IO, the treatment for 24h resulted in an increase of DNA damage. FCS slightly protected PBMCs from the genotoxic effects induced by IO and BO, whilst no such effect was noted for the other compounds. Overall, the dose-dependent effects that were seen allowed us to define a genotoxicity scale for the different epoxides as follows: SO>EB>DEB>IO>PO>BO, which is in partial agreement with the International Agency for Research on Cancer (IARC) classification of the carcinogenic hazards.

  2. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3 cells

    Directory of Open Access Journals (Sweden)

    Hussein Al Ali SH

    2012-07-01

    Full Text Available Samer Hasan Hussein Al Ali,1 Mothanna Al-Qubaisi,2 Mohd Zobir Hussein,1,3 Maznah Ismail,2,4 Zulkarnain Zainal,1 Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, Universiti Putra, Malaysia; 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w. The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 µg/mL, respectively.Keywords: cetirizine hydrochloric acid

  3. Development and characterization of a monoclonal antibody specific for human basophils and the identification of a unique secretory product of basophil activation.

    Science.gov (United States)

    McEuen, A R; Buckley, M G; Compton, S J; Walls, A F

    1999-01-01

    Despite increasing evidence that basophils can infiltrate into inflamed tissues during allergic reactions, determination of the extent of infiltration and elucidation of their role in allergic disease has been frustrated by the lack of reliable means for detecting this cell type in tissues. In the present study, we report on a new monoclonal antibody specific for basophils and on the initial characterization of the antigen it recognizes. Basophils were isolated from peripheral blood by Percoll density gradient centrifugation and a positive-selection immunomagnetic procedure and injected into mice to produce monoclonal antibodies. A hybridoma clone, designated BB1, secreted antibody of the IgG2a isotype; this antibody bound selectively to basophils on immunocytochemistry but did not react with any other cell type or tissue structure, although it did stain a proportion of cells from the basophilic cell line KU812F. In sections of mixed populations of peripheral blood cells, similar numbers of cells stained with Alcian blue dye and BB1 over a wide range of basophil purity. BB1 antibody was effective in identifying basophils in sections of mixed cells or in tissues after fixation with ethanol, Carnoy's solution, or formalin. Staining of basophils with BB1 gave a granular appearance, although flow cytometry indicated that some antigen was also present on the surface of the cell. Activation of these cells with anti-IgE antibody or with the calcium ionophore A23187 provoked release of the antigen in parallel with that of histamine. BB1 antibody did not, by itself, stimulate histamine release. The molecular mass of the antigen was determined on Hedrick-Smith gels to be 124+/-11 kd. This new monoclonal antibody will be a valuable experimental tool in future studies, allowing the reliable detection of basophils in tissues of patients with allergic and chronic inflammatory disease; in addition, the antigen it identifies has potential as a unique marker of basophil activation.

  4. Basophil competence during hookworm (Necator americanus) infection.

    Science.gov (United States)

    Pritchard, David I; Hooi, Doreen S W; Brown, Alan; Bockarie, Moses J; Caddick, Rebecca; Quinnell, Rupert J

    2007-11-01

    A popular hypothesis to explain parasite survival in the presence of a pronounced T helper 2 phenotype in helminth-parasitized populations has been Fc epsilonRI blockade by parasite-induced polyclonal IgE. To begin to test the hypothesis that Fc epsilonRI-bearing cells would be refractory to activation in parasitized populations, we investigated basophil function in 43 individuals from a hookworm endemic area. Study individuals had high levels of total IgE and eosinophilia and a mean hookworm burden of 2,257 epg. Basophils from all members of this parasitized population were shown to release histamine to a number of agonists, including anti IgE and a hookworm allergen, calreticulin. These data would indicate that Fc epsilonRI blockade at the level of the basophil did not occur in this parasitized population despite the presence of possible immunologic blocking agents. This would suggest that this effector arm of the T helper 2 phenotype remains operative in infected populations.

  5. Bcl-xL and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Henning Schulze-Bergkamen; Steffen Heeger; Peter R Galle; Markus Moehler; Roland Ehrenberg; Lothar Hickmann; Binje Vick; Toni Urbanik; Christoph C Schimanski; Martin R Berger; Arno Schad; Achim Weber

    2008-01-01

    AIM: To explore the role of Bd-x,and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities.METHODS: BCl-XL and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCR and immunohistochemistry.Bcl-x,and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids,respectively.After modulation of protein expression,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor receptor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibitor,or with the death receptor ligand TRAIL.Apoptosis induction and cell viability were analyzed.RESULTS: Here we show that in human CRC tissue and various CRC cell lines both Bcl-x,and Mcl-1 are expressed.Bcl-x,expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level.Mcl-1 mRNA expression was significantly lower in malignant tissues.However,protein expression was slightly higher.Viability rates of CRC cells were significantly decreased after knock down of Bcl-XL expression,and,to a lower extent,after knock down of Mcl-1 expression.Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin- and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis.On the other hand,upregulation of Bcl-XL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis.EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells.Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Hcl-1 and Bcl-xL expression.More strikingly,CD95- and TRAIL-induced apoptosis was increased by Bcl-xL knock down.CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC

  6. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A. [Ulm Univ. (Germany). Abt. Nuklearmedizin; Bunjes, D.; Doehner, H. [Abteilung Innere Medizin III, Haematologie und Onkologie, Universitaetsklinikum Ulm (Germany); Martin, H.; Bergmann, L. [Klinik fuer Haematologie und Onkologie, Johann-Wolfgang-Goethe Universitaet Frankfurt (Germany)

    2001-07-01

    Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ({sup 188}Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2{+-}2.1 (range 6.9-15.8) GBq {sup 188}Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4{+-}5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking {sup 188}Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

  7. Leukaemic cells from chronic lymphocytic leukaemia patients undergo apoptosis following microtubule depolymerization and Lyn inhibition by nocodazole.

    Science.gov (United States)

    Frezzato, Federica; Trimarco, Valentina; Martini, Veronica; Gattazzo, Cristina; Ave, Elisa; Visentin, Andrea; Cabrelle, Anna; Olivieri, Valeria; Zambello, Renato; Facco, Monica; Zonta, Francesca; Cristiani, Andrea; Brunati, Anna Maria; Moro, Stefano; Semenzato, Gianpietro; Trentin, Livio

    2014-06-01

    Functional abnormalities of chronic lymphocytic leukaemia (CLL) cells may be related to the microtubular network of cell cytoskeleton; specifically tubulin involvement in cells after B-cell receptor engagement. As microtubule inhibitors could represent a therapeutic strategy for CLL, this study investigated the capability of nocodazole, a synthetic depolymerizing agent, to kill CLL leukaemic cells. We demonstrated that nocodazole was highly specific for the in vitro induction of apoptosis in leukaemic cells from 90 CLL patients, without affecting the viability of T-cells and/or mesenchymal stromal cells (MSCs) recovered from the same patients. Nocodazole was observed to overcome the pro-survival signals provided by MSCs. Competing with ATP for the nucleotide-binding site, nocodazole has been observed to turn off the high basal tyrosine phosphorylation of leukaemic cells mediated by the Src-kinase Lyn. Considering that most anti-microtubule drugs have limited clinical use because of their strong toxic effects, the high selectivity of nocodazole for leukaemic cells in CLL and its capability to bypass microenvironmental pro-survival stimuli, suggests the use of this inhibitor for designing new therapeutic strategies in CLL treatment.

  8. OM-X®, Fermented Vegetables Extract Suppresses Antigen-Stimulated Degranulation in Rat Basophilic Leukemia RBL-2H3 Cells and Passive Cutaneous Anaphylaxis Reaction in Mice.

    Science.gov (United States)

    Itoh, Tomohiro; Miyake, Yasuyoshi; Kasashima, Takuya; Shimomiya, Yoshie; Nakamura, Yuki; Ando, Masashi; Tsukamasa, Yasuyuki; Takahata, Muneaki

    2015-09-01

    OM-X® is a hand-made and naturally manufactured probiotic supplement. This fermented food product is made from vegetables, fruits, seaweeds and mushrooms, using 12 strains of lactic acid bacteria and bifidobacteria. OM-X® is also known to have beneficial health properties, and some of its components show effects on antigen (Ag)-stimulated degranulation activity, indicating that OM-X® may be useful in the treatment of allergy responses and symptoms. In this study, we evaluated the inhibitory effects of OM-X® on Ag-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells, clarified the underlying mechanisms, and determined the active compounds in OM-X® for suppression of degranulation. Treatment with OM-X® gradually suppressed Ag-stimulated degranulation throughout the maturation period. OM-X® also gradually produced melanoidins by lactic acid bacterial fermentation during the maturation process. There was a high correlation between the suppression levels of Ag-stimulated degranulation and the browning of OM-X®. Furthermore, the inhibition of Ag-stimulated degranulation by OM-X® was found to be partially due to the direct inactivation of NADPH oxidase. To elucidate the in vivo effects of OM- X®, type I allergy model mice were orally administered with OM-X®, and the passive cutaneous anaphylaxis (PCA) reaction was measured. OM-X® intake remarkably suppressed the PCA reaction. Taken together, our findings suggest that OMX® could be a beneficial food to ameliorate allergic reactions.

  9. JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells.

    Science.gov (United States)

    Wu, Haitao; Qi, Hang; Iwasaki, Dai; Zhu, Beiwei; Shimoishi, Yasuaki; Murata, Yoshiyuki; Nakamura, Yoshimasa

    2009-10-01

    (-)-Epigallocatechin-3-gallate (EGCG) has been reported to possess a wide range of biological and pharmacological properties. In this study, we investigated the effects of EGCG on IL-13 gene expression in human basophilic KU812 cells. The IL-13 mRNA expression level was dose-dependently increased by treatment with EGCG (5-20 microM) for 1 h and additional incubation in a medium for 23 h. EGCG significantly increased the intracellular peroxide level as detected by the peroxide-sensitive probe 2',7'-dichlorodihydrofluorescein diacetate. A pharmacological experiment using catalase and a structure-activity relationship study revealed that the exogenously produced H(2)O(2) significantly, but partially, contributed to the IL-13 expression as well as the intracellular oxidative status. Furthermore, EGCG at the concentration required for IL-13 up-regulation activated c-Jun NH(2)-terminal kinase (JNK), but not extracellular signal-regulated protein kinase or p38 mitogen-activated protein kinase in KU812 cells. Transfection of a JNK-specific siRNA as well as treatment with a JNK-specific inhibitor, SP600125, significantly reduced the EGCG-induced IL-13 mRNA expression, by 47.1 and 44.6%, respectively. In addition, we observed the nuclear translocation, mRNA up-regulation, and activation of DNA binding with the IL-13 promoter of nuclear factor of activated T cells (NFATc1) in the EGCG-treated cells. These data provide biological evidence that EGCG induces IL-13 mRNA expression via the JNK-dependent NFATc1 pathway in KU812 cells.

  10. Contribution of basophils to cutaneous immune reactions and Th2-mediated allergic responses

    Directory of Open Access Journals (Sweden)

    Atsushi eOtsuka

    2015-08-01

    Full Text Available Basophils are potent effector cells of innate immunity and also play a role in T helper 2 (Th2-mediated allergic responses. But, although their in vitro functions are well studied, their in vivo functions remain largely unknown. However, several mouse models of basophil depletion have recently been developed and used to investigate basophil functions. For example, in a croton oil-induced model of irritant contact dermatitis in conditionally basophil-depleted transgenic mice, we found that basophils rapidly infiltrate inflamed skin and subsequently induce infiltration of eosinophils. We also showed that basophils induce Th2 skewing upon epicutaneous sensitization with various haptens and peptide antigens. Intriguingly, basophils also promoted Th2 polarization upon protein antigen exposure in the presence of dendritic cells (DCs. The dermal DC subset associated with Th2 skewing was recently identified as CD301b+ DC. Such studies with basophil-deficient mouse models have significantly improved our understanding of the mechanisms involved in human immune-related diseases. In this review, we will focus on the relative contribution of basophils and DCs to Th2-mediated allergic responses.

  11. Development of a microarray-based method to detect exposure of human basophils to IL-3.

    Science.gov (United States)

    MacGlashan, Donald

    2012-11-30

    Human basophils are an accessible participant of the human allergic reaction. There is natural variation in various functional endpoints and in signaling molecule expression but there has been only a limited effort to place this information in the context of mRNA expression profiles. The goal of these studies was to develop gene transcript profiles associated with IL-3 exposure for use in probing basophil phenotypes. Highly purified human basophils were cultured under several conditions and the cells subsequently analyzed by microarray analysis of gene transcript expression. Basophils were cultured with or without IL-3 for 24 h and the expression profile, relative to pre-culture, analyzed for transcripts that act in a reciprocal fashion depending on the condition. A 51-gene transcript set was identified that was composed of 34 transcripts that increased with IL-3 and decreased without IL-3 and a further 17 transcripts that did the reverse. This set of transcripts was validated on two microarray chips. The changes induced by IL-3 were stable in time, with 3 day cultures generating a signature concordant with 1 day cultures. The inverted nature of the response to ±IL-3 suggested that the normal circulating basophil is balanced between a state of high and low IL-3 exposure and thus is very sensitive to changes in IL-3. For example, the basophil could detect the early generation of IL-3 that follows IgE-mediated stimulation of basophils. When this signature tool was applied to freshly isolated basophils, it was observed that the signature was similar for the same subjects' basophil sampled weeks apart. It was also shown that the 51-gene transcript was insensitive to the method of preparing purified basophils. Finally, these studies provided an estimate for the normal in vivo exposure of circulating basophils to IL-3 or IL-3-like functionality. These studies identified an IL-3 signature to probe changes in basophils occurring in vivo.

  12. Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Akahane, Koshi; Li, Zhaodong; Etchin, Julia; Berezovskaya, Alla; Gjini, Evisa; Masse, Craig E; Miao, Wenyan; Rocnik, Jennifer; Kapeller, Rosana; Greenwood, Jeremy R; Tiv, Hong; Sanda, Takaomi; Weinstock, David M; Look, A Thomas

    2017-04-01

    Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage. Activation of p38 MAPK occurred within 1 h of NDI-031301 treatment and was responsible for NDI-031301-induced T-ALL cell death, as pharmacological inhibition of p38 MAPK partially rescued apoptosis induced by TYK2 inhibitor. Finally, daily oral administration of NDI-031301 at 100 mg/kg bid to immunodeficient mice engrafted with KOPT-K1 T-ALL cells was well tolerated, and led to decreased tumour burden and a significant survival benefit. These results support selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL.

  13. JNK and NFκB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells.

    Science.gov (United States)

    Calviño, Eva; Tejedor, M Cristina; Sancho, Pilar; Herráez, Angel; Diez, José C

    2015-06-01

    The relationship between the mitogen-activated protein kinase response, nuclear factor-κB (NFκB) expression and the apoptosis in human acute promyelocytic leukaemia NB4 cells treated with vinblastine was investigated in this work. Cell viability, subdiploid DNA and cell cycle were analysed by propidium iodide permeability and flow cytometry analyses. Apoptosis was determined by annexin V-Fluorescein isothiocyanate assays. Western-blot analysis was used for determination of expression levels of apoptotic factors (p53, Bax and Bcl2), intracellular kinases [serine/threonine-specific protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK)], NFκB factor and caspases. Electrophoretic mobility shift assay was usefully applied to study DNA-NFκB interaction. In NB4 cells, vinblastine produces alteration of p53 and DNA fragmentation. Vinblastine treatment had an antiproliferative effect via the induction of apoptosis producing Bax/Bcl-2 imbalance. Vinblastine treatment suppressed NFκB expression and depressed NFκB-DNA binding activity while maintaining JNK activation that subsequently resulted in apoptotic response through caspase-dependent pathway. Our study provides a possible anti-cancer mechanism of vinblastine action on NB4 cells by deregulation of the intracellular signalling cascade affecting to JNK activation and NFκB expression. Moreover, JNK activation and NFκB depression can be very significant factors in apoptosis induction by vinblastine.

  14. Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia.

    Directory of Open Access Journals (Sweden)

    Edwin D Hawkins

    Full Text Available In epithelial and stem cells, lethal giant larvae (Lgl is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1⁻/⁻ mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts.

  15. Direct interaction of Syk and Lyn protein tyrosine kinases in rat basophilic leukemia cells activated via type I Fc epsilon receptors.

    Science.gov (United States)

    Amoui, M; Dráberová, L; Tolar, P; Dráber, P

    1997-01-01

    Activation of rat mast cells through the receptor with high affinity for IgE (Fc epsilonRI) requires a complex set of interactions involving transmembrane subunits of the Fc epsilonRI and two classes of nonreceptor protein tyrosine kinase (PTK). the Src family PTK p53/p56(lyn) (Lyn) and the Syk/ZAP-family PTK p72(syk) (Syk). Early activation events involve increased activity of Lyn and Syk kinases and their translocation into membrane domains containing aggregated Fc epsilonRI, but the molecular mechanisms responsible for these changes have remained largely unclear. To determine the role of Fc epsilonRI subunits in this process, we have analyzed Syk- and Lyn-associated proteins in activated rat basophilic leukemia (RBL) cells and their variants deficient in the expression of Fc epsilonRI beta or gamma subunits. Sepharose 4B gel chromatography of postnuclear supernatants from Nonidet-P40-solubilized antigen (Ag)- or pervanadate-activated RBL cells revealed extensive changes in the size of complexes formed by Lyn and Syk kinases and other cellular components. A fusion protein containing Src homology 2 (SH2) and SH3 domains of Lyn bound Syk from lysates of nonactivated RBL cells; an increased binding was observed when lysates from Ag- or pervanadate-activated cells were used. A similar amount of Syk was bound when lysates from pervanadate-activated variant cells deficient in the expression of Fc epsilonRI beta or gamma subunits were used, suggesting that Fc epsilonRI does not function as the only intermediate in the formation of the Syk-Lyn complexes. Further experiments have indicated that Syk-Lyn interactions occur in Ag-activated RBL cells under in vivo conditions and that these interactions could involve direct binding of the Lyn SH2 domain with phosphorylated tyrosine of Syk. The physical association of Lyn and Syk during mast-like cell activation supports the recently proposed functional cooperation of these two tyrosine kinases in Fc epsilonRI signaling.

  16. Heterogeneous X-ray survival characteristics of lymphocytes in prolymphocytic leukaemia. Mathematical analysis distinguishing delayed cell death and true radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, A.E.R.; O' Connor, T.W.E.; Slater, N.G.P. (Division of Haematology, United Medical and Dental Schools of Guy' s and St. Thomas' Hospitals, London (United Kingdom)); Peel, W.E. (Computing Services, Manchester Metropolitan University, Manchester (United Kingdom))

    1994-10-01

    The survival of non-dividing (G[sub 0]) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ('interphase death') are seen. Counts of surviving cells well therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical 'single-hit' target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T[sub 172] values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). B ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorized as resistant to elimination by radiotherapy. (au) (30 refs.).

  17. Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

    Science.gov (United States)

    Olme, C-H; Finnon, R; Brown, N; Kabacik, S; Bouffler, S D; Badie, C

    2013-10-01

    The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

  18. Basophil degranulation induced by oral poison ivy antigen.

    Science.gov (United States)

    Shelley, W B; Resnik, S S

    1965-08-01

    Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were challenged with graded oral doses of ivy extract. In each instance the circulating basophil leukocytes showed significant degranulation within one hour of challenge. This finding was interpreted as evidence of the presence of immediate-type circulating antibody to ivy antigen in these subjects. No drop in the absolute basophil count was noted, but with higher oral doses the degranulation persisted for several days. Thirteen control subjects showed no change in the basophil morphology or count, indicating that the resin at these levels was not toxic to this cell. All but one of the sensitive subjects showed objective patch test evidence of hyposensitization following the intensive three-week course of oral poison ivy antigen.

  19. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  20. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  1. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli.

    Science.gov (United States)

    Sakata, Katsumi; Saito, Toshiyuki; Ohyanagi, Hajime; Okumura, Jun; Ishige, Kentaro; Suzuki, Harukazu; Nakamura, Takuji; Komatsu, Setsuko

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state-space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical "external stimulus-induced information loss" model of biological systems.

  2. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  3. Microglia-derived interleukin-6 and leukaemia inhibitory factor promote astrocytic differentiation of neural stem/progenitor cells.

    Science.gov (United States)

    Nakanishi, Masaya; Niidome, Tetsuhiro; Matsuda, Satoru; Akaike, Akinori; Kihara, Takeshi; Sugimoto, Hachiro

    2007-02-01

    Neural stem/progenitor cells (NSPCs) proliferate and differentiate depending on their intrinsic properties and local environment. It has been recognized that astrocytes promote neurogenic differentiation of NSPCs, suggesting the importance of cell-cell interactions between glial cells and NSPCs. Recent studies have demonstrated that microglia, one type of glial cells, play an important role in neurogenesis. However, little is known about how activated microglia control the proliferation and differentiation of NSPCs. In this study, we investigated the possibility that microglia-derived soluble factors regulate the behaviour of NSPCs. To this end, NSPCs and microglial cultures were obtained from rat embryonic day 16 subventricular zone (SVZ) and rat postnatal 1 day cortex, respectively, and the conditioned medium from microglia was prepared. Microglial-conditioned medium had no significant effect on the proliferation of NSPCs. In contrast, it increased the percentage of cells positive for a marker of astrocytes, glial fibrillary acidic protein (GFAP) during differentiation. The induction of astrocytic differentiation by microglial-conditioned medium was reduced by the inhibition of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, microglia-derived interleukin (IL)-6 and leukaemia inhibitory factor (LIF) were identified as essential molecules for this astrocytic differentiation using neutralizing antibodies and recombinant cytokines. Our results suggest that microglia as well as astrocytes contribute to the integrity of the local environment of NSPCs, and at least IL-6 and LIF released by activated microglia promote astrocytic differentiation of NSPCs via the activation of the JAK/STAT and MAPK pathways.

  4. The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells.

    Science.gov (United States)

    Cellai, C; Balliu, M; Laurenzana, A; Guandalini, L; Matucci, R; Miniati, D; Torre, E; Nebbioso, A; Carafa, V; Altucci, L; Romanelli, M N; Paoletti, F

    2012-08-01

    Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++)--chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4--but not (R)-2--caused G0/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy.

  5. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy.

    Science.gov (United States)

    Vanna, R; Ronchi, P; Lenferink, A T M; Tresoldi, C; Morasso, C; Mehn, D; Bedoni, M; Picciolini, S; Terstappen, L W M M; Ciceri, F; Otto, C; Gramatica, F

    2015-02-21

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducible. Therefore, the development of subjective and potentially automatable methods for the recognition of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and erhytroblasts, which have to be counted for a correct diagnosis and morphological classification of AML and MDS. BM samples from patients affected by four different AML subtypes, mostly characterized by the presence of the four subpopulations selected for this study, were analyzed. First, each cell was scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate an accurate description of morphological features characteristic of each subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted the automatic discrimination and localization of the nucleus, the cytoplasm, myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman fingerprint of each cell was analysed by multivariate analysis (principal component analysis and linear discriminant analysis) in order to study the typical vibrational features of each subpopulation and also for the automatic recognition of cells. The leave-one-out cross validation of a Raman-based classification model demonstrated the correct classification of myeloblasts, promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%. Normal and abnormal promyelocytes were distinguished with 95% accuracy. The overall classification accuracy considering the four subpopulations was 98%. This proof-of-concept study shows that Raman micro-spectroscopy could be a valid approach for developing label-free, objective and automatic

  6. TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Middeke, Jan M; Herold, Sylvia; Rücker-Braun, Elke; Berdel, Wolfgang E; Stelljes, Matthias; Kaufmann, Martin; Schäfer-Eckart, Kerstin; Baldus, Claudia D; Stuhlmann, Reingard; Ho, Anthony D; Einsele, Hermann; Rösler, Wolf; Serve, Hubert; Hänel, Mathias; Sohlbach, Kristina; Klesse, Christian; Mohr, Brigitte; Heidenreich, Falk; Stölzel, Friedrich; Röllig, Christoph; Platzbecker, Uwe; Ehninger, Gerhard; Bornhäuser, Martin; Thiede, Christian; Schetelig, Johannes

    2016-03-01

    Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.

  7. Chronic lymphocytic leukaemia

    Science.gov (United States)

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  8. Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

    Science.gov (United States)

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio

    2006-02-03

    Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

  9. Use of humanized rat basophilic leukemia reporter cell lines as a diagnostic tool for detection of allergen-specific IgE in allergic patients: time for a reappraisal?

    Science.gov (United States)

    Falcone, Franco H; Alcocer, Marcos J C; Okamoto-Uchida, Yoshimi; Nakamura, Ryosuke

    2015-11-01

    The interaction between allergens and specific IgE is at the heart of the allergic response and as such lies at the center of techniques used for diagnosis of allergic sensitization. Although serological tests are available, in vivo tests such as double-blind placebo-controlled food challenges (DBPCFC) and skin prick test (SPT) associated to the patients' clinical history are still the main guides to clinicians in many practices around the world. More recently, complex protein arrays and basophil activation tests, requiring only small amounts of whole blood, have been developed and refined, but are yet to enter clinical practice. Similarly, the use of rat basophilic leukemia (RBL) cell lines for detection of allergen-specific IgE has been made possible by stable transfection of the human FcεRI α chain into this cell line more than 20 years ago, but has not found widespread acceptance among clinicians. Here, we review the perceived limitations of diagnostic applications of humanized RBL systems. Furthermore, we illustrate how the introduction of reporter genes into humanized RBL cells is able to overcome most of these limitations, and has the potential to become a new powerful tool to complement the armamentarium of allergists. A demonstration of the usefulness of humanized RBL reporter systems for elucidation of complex IgE sensitization patterns against wheat proteins and a section on the use of fluorescence-based reporter systems in combination with allergen arrays close the review.

  10. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  11. Trisomy 19 and T(9;22 In a Patient with Acute Basophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Alicia Rojas-Atencio

    2011-01-01

    Full Text Available We report a case of acute basophilic leukemia with two coexisting clonal abnormalities, t(9;22 and trisomy 19. The blast showed positive reaction with myeloperoxidase but negative reaction with chloroacetate esterase and acid phosphatase. Metachromatic features of the blast were observed with toluidine blue stain. Ultrastructure study showed the presence of azurophilic granules in basophils and blast mast cells. Conventional and molecular cytogenetic studies revealed, t(9;22 with BCR/ABL positive and trisomy 19 in all metaphase cells. To our knowledge, this paper here is the first to present acute basophilic leukemia with trisomy 19 and t(9;22.

  12. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...

  13. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy

    NARCIS (Netherlands)

    Vanna, R.; Ronchi, P.; Lenferink, A.T.M.; Terstappen, L.W.M.M.; Tresoldi, C.; Morasso, C.; Mehn, D.; Bedoni, M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2015-01-01

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducib

  14. Bloodstream infection caused by Acinetobacter junii in a patient with acute lymphoblastic leukaemia after allogenic haematopoietic cell transplantation.

    Science.gov (United States)

    Cayô, Rodrigo; Yañez San Segundo, Lucrecia; Pérez del Molino Bernal, Inmaculada Concepción; García de la Fuente, Celia; Bermúdez Rodríguez, Maria Aranzazu; Calvo, Jorge; Martínez-Martínez, Luis

    2011-03-01

    Acinetobacter junii is a rare human pathogen associated with bacteraemia in neonates and paediatric oncology patients. We present a case of A. junii causing bacteraemia in an adult transplant patient with leukaemia. The correct identification of Acinetobacter species can highlight the clinical significance of the different species of this genus.

  15. Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

    Energy Technology Data Exchange (ETDEWEB)

    Nishikado, Hideto [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Laboratory of Proteomics and Biomolecular Science, BioMedical Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Ogawa, Hideoki; Okumura, Ko [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Takai, Toshiro, E-mail: t-takai@juntendo.ac.jp [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan)

    2015-05-01

    Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity.

  16. Basophil-activation tests in hymenoptera allergy

    NARCIS (Netherlands)

    Dubois, Anthony E. J.; van der Heide, Sicco

    2007-01-01

    The measurement of basophil-activation markers may be useful in detecting IgIE-mediated sensitization but the relevance for application of the basophil-activation test in prediction of clinical reactivity in Hymenoptera allergy is very limited. For this reason, this test currently has no established

  17. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  18. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility.

    Science.gov (United States)

    Smaniotto, Salete; Schneider, Elke; Goudin, Nicolas; Bricard-Rignault, Rachel; Machavoine, François; Dardenne, Mireille; Dy, Michel; Savino, Wilson

    2013-01-01

    Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively), we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  19. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility.

    Directory of Open Access Journals (Sweden)

    Salete Smaniotto

    Full Text Available Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1, which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively, we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  20. Basophil sensitivity through CD63 or CD203c is a functional measure for specific immunotherapy

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    Dahl Ronald

    2010-02-01

    Full Text Available Abstract Background Subcutaneous Immunotherapy (SCIT modifies the allergic response and relieves allergic symptoms. SCIT is the only and a very effective treatment for insect venom allergy. We hypothesized that basophil sensitivity, measured through the basophil activation test, would decrease during SCIT up dosing. Expression of CD203c was compared to CD63 as marker for basophil activation, using a Bland Altman plot and ROC curves. Methods Patients (n = 18 starting subcutaneous SCIT for wasp allergy with an up dosing scheme of 7 to 11 weeks were enrolled. Heparinised blood samples were drawn at weeks 1-4, 7 and at the first maintenance visit. Basophils were stimulated at 7 log dilutions of V. vespula allergen for 15 min, and were stained with CD203c and CD63. Basophils were identified as CD203c+ leukocytes, and the proportion of CD63+ and CD203c+ cells were plotted against allergen concentration. A sigmoid curve was fitted to the points, and the allergen concentration at which half of the maximal activation was achieved, LC50, was calculated. In another series of experiments, LC50 calculated in whole blood (AP was subtracted from LC50 calculated with basophils suspended in plasma from a nonatopic donor (HS to determine the protective effect of soluble factors in blood of patients treated with SCIT. Results Heparin blood basophil activation was similar through CD63 and CD203c. Basophils were significantly more sensitized three weeks after initiation of SCIT compared to baseline (p Conclusion Basophil activation is a versatile and sensitive tool that measures changes in the humoral immune response to allergen during SCIT.

  1. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

    Science.gov (United States)

    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  2. 2'-Nitroflavone induces apoptosis and modulates mitogen-activated protein kinase pathways in human leukaemia cells.

    Science.gov (United States)

    Cárdenas, Mariano G; Blank, Viviana C; Marder, Mariel N; Roguin, Leonor P

    2012-09-01

    The cytotoxic activity of 2'-nitroflavone was evaluated in different haematological cancer cell lines and its mechanism of action was further studied in HL-60 cells. 2'-Nitroflavone arrested the cell cycle at the G(2)/M phase and induced an apoptotic response characterized by an increase in the sub-G1 fraction of cells, a typical DNA ladder fragmentation, chromatin condensation and the detection of cells stained with Annexin V. Apoptosis was dependent on the activation of at least caspase-8, caspase-9 and caspase-3. The involvement of the death receptor pathway was indicated by the upregulation of both the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor (DR5). We also showed that 2'-nitroflavone increased the expression levels of Bax and induced the release of cytochrome C to cytosol, suggesting the participation of the mitochondria-dependent pathway. When mitogen-activated protein kinases pathways were studied, it was found that p38 and c-Jun NH(2)-terminal kinase (JNK) pathways were activated by 2'-nitroflavone in HL-60 cells, whereas the phosphorylation levels of extracellular signal-regulated kinases (ERK) 1/2 decreased significantly. In addition, whereas both pharmacological inhibition of JNK and downregulation of JNK expression by RNA interference reduced the nitroflavone growth-inhibitory activity and the apoptotic effect, contrasting results were obtained when the ERK1/2 pathway was inhibited, and no effect was observed in the presence of a specific inhibitor of p38 mitogen-activated protein kinase. These findings show for the first time the antitumour action of 2'-nitroflavone in haematological cancer cell lines and suggest that both JNK and ERK1/2 cascades are involved in the apoptotic response induced by 2'-nitroflavone in HL-60 cells.

  3. Diagnosis of clavulanic acid allergy using basophil activation and leukotriene release by basophils.

    Science.gov (United States)

    Longo, N; Gamboa, P M; Gastaminza, G; Audícana, M T; Antepara, I; Jaúregui, I; Sanz, M L

    2008-01-01

    Clavulanic acid is a potent inhibitor of B-lactamase that is increasingly prescribed in association with amoxicillin. We report 2 cases of patients who experienced pruritus, wheals, and angioedema after oral intake of amoxicillin/clavulanic acid. Routine skin tests for B-lactam antibiotics and specific immunoglobulin (Ig) E were negative in both patients. Analysis of CD63 expression by the basophil activation test (BAT) using flow cytometry and of sulphidoleukotriene (sLT) release by basophils using the cellular allergen stimulation test (CAST) revealed significant positive responses with amoxicillin/clavulanic acid and with clavulanic acid, and negative responses with amoxicillin and other beta-lactam antibiotics. In addition, cultured CD3+CD4+ cells showed a significant increase in the expression of CD69, CD25, and HLA-DR in the presence of clavulanic acid. Both patients tolerated therapeutic doses of amoxicillin. BAT and CAST are useful ex vivo procedures for the detection of specific IgE-mediated allergy to clavulanic acid, especially for patients with negative skin test results.

  4. Persistence of Natural Killer (NK cell lymphocytosis with hyposplenism without development of leukaemia

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    Khan Sujoy

    2005-09-01

    Full Text Available Abstract Background Natural killer (NK cell lymphocytosis usually has an indolent course and can progress into massive lymphocytosis with development of cytopenias and neoplastic diseases. NK-cells usually express one or more "NK-associated" antigens (CD16, CD56, CD57. Reactive expansions are seen in autoimmune diseases, viral infections, solid tumours and non-Hodgkin's lymphoma. Case presentation We report a lady with a benign clinical course over 10 years and persistent CD8+/CD3-/CD57+/CD16+ LGL proliferation with presence of Howell-Jolly bodies (functional hyposplenism, an association not previously described. Conclusion We discuss the possible causes of clonal expansion and conclude that this may be part of the spectrum of immune dysregulation associated with NK-cell lymphocytosis.

  5. IN SUBJECTS ALLERGIC TO GRASS POLLEN, BASOPHIL SENSITIVITY DECREASES DURING SUBCUTANEOUS IMMUNOTHERAPY DUE TO BOTH HUMORAL FACTORS AND CELLULAR DESENSITIZATION

    DEFF Research Database (Denmark)

    Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen

    2011-01-01

    with allergic rhino-conjunctivitis with basophil activation tests (BAT). Methods: We have randomized 24 patients to a treatment (18) and an open control group (6). Repeated BAT were performed at baseline and througout treatment. Heparinized blood was centrifuged, plasma was removed, the cells washed twice......, then reconstituted with plasma from the present and baseline visit, and medium. The cells were 406 ESCCA AND ICyS ABSTRACTS Cytometry Part B: Clinical Cytometry incubated with log dilutions of grass pollen extract and washed again. Basophil activation was measured as the percentage of CD63 expression on CD193 þ...... basophils. The LC50 was calculated as the log of the allergen concentration leading to half maximum basophil activation. Specific IgE and IgG4 was measured using ISAC panel. Results: We found a 15-fold reduction in basophil sensitivity in the treated group during updosing, compared to their baseline...

  6. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  7. Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia

    Directory of Open Access Journals (Sweden)

    Tommasina Guglielmelli

    2009-01-01

    Full Text Available Plasma cell leukemia (PCL is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least 2×109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005. Thalidomide, bortezomib and lenalidomide (Revlimid have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006. In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007, although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008. We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.

  8. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules.

  9. Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission.

    Science.gov (United States)

    van Kooten Niekerk, Peter B; Petersen, Charlotte C; Nyvold, Charlotte G; Ommen, Hans B; Roug, Anne S; Nederby, Line; Hokland, Peter; Kjeldsen, Eigil

    2014-01-01

    The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34(+) stem cell and progenitor cell subpopulations were isolated by fluorescence-activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph(+) ) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4-log reduction in BCR-ABL1 expression (MR(4) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR(4) , and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.

  10. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Silconi Žana Besser

    2015-09-01

    Full Text Available Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity, ototoxicity, and neurotoxicity. Although cisplatin is one of the most successful anticancer drugs to date, its biochemical mechanism of action is still unclear. Cisplatin is generally accepted as having the ability to interact with the purine bases on the DNA, causing DNA damage, interfering with DNA repair mechanisms, and subsequently inducing apoptosis in cancer cells.

  11. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

    Science.gov (United States)

    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  12. Cutaneous B-cell chronic lymphocytic leukaemia resembling a granulomatous rosacea.

    Science.gov (United States)

    di Meo, Nicola; Stinco, Giuseppe; Trevisan, Giusto

    2013-10-16

    B-cell chronic lymphocytic leukemia (B-CLL) is a low-grade lymphoproliferative disease. Cutaneous involvement of B-CLL is limited and, in most cases, it represents non-specific manifestations related to an impaired immune system. Leukemic skin infiltrates (leukemia cutis) occur in 4-20% of patients. Herein we report the case of a 65-year-old woman with B-CLL presenting with papular, nodular, and plaque skin infiltrates affecting the nose, mimicking granulomatous rosacea. We discuss several aspects of rare cutaneous manifestations of B-CLL involving the face.

  13. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

    2016-01-01

    on follow-up testing in 15 patients a median of 350 days later. T cell aberrant loss of CD5 or gain of expression of CD16 and CD94 were common (19/42, 45%). In comparison, 2/15 (14%) age-matched patients with dermatomyositis, polymyositis, or necrotizing myopathy, and 0/20 (0%) age-matched healthy subjects...... expansions. Cross-sectional data suggested more aggressive disease in patients with such expansions than without. Muscle immunohistochemistry demonstrated invasion of large granular lymphocytes into muscle in 15/15 inclusion body myositis patients but in only 1/28 patients with dermatomyositis...

  14. Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive

    Directory of Open Access Journals (Sweden)

    Magalie Joris

    2012-01-01

    Full Text Available Mast cell leukemia (MCL is a rare and aggressive disease with poor prognosis and short survival time. D816V c-KIT mutation is the most frequent molecular abnormality and plays a crucial role in the pathogenesis and development of the disease. Thus, comprehensive diagnostic investigations and molecular studies should be carefully carried out to facilitate the therapeutic choice. A MCL patient’s case with rare phenotypic and genotypic characteristics is described with review of major clinical biological and therapeutic approaches in MCL.

  15. Responsiveness of basophil granulocytes of horses suffering from chronic obstructive pulmonary disease to various allergens.

    Science.gov (United States)

    Dirscherl, P; Grabner, A; Buschmann, H

    1993-10-01

    As basophils are the major effector cells of allergic reactions, confirmation of the allergic etiology of chronic obstructive pulmonary disease (COPD) was sought by the demonstration of a specific in vitro response of equine basophilic blood cells to some potential allergens (Aspergillus, Cladosporidium, Mucor, Penicillium, extracts of dust particles of hay and straw). The allergen induced degranulation of basophils and the histamine and protease release from basophils during incubation with the allergens were tested. By evaluating the results obtained from 14 COPD horses and eight controls it could be shown that the sensitivity of the basophils of affected horses was increased, particularly against the allergen extract of Mucor mucedo and Mucor spinosus. Further a greater percentage of COPD horses reacted positively with the Mucor allergen extract. The mitogenic stimulation of lymphocytes by PHA and by the allergen extracts used gave comparable results in affected and control horses. Thus the in vitro stimulation of basophils may be an easily to perform testing device for the identification of potential allergens involved in the pathogenesis of equine COPD.

  16. In vitro experimental {sup 211}At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

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    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H. [Hanover University School of Medicine, Department of Nuclear Medicine, Hanover (Germany); Froemke, Cornelia [Hanover University School of Medicine, Department of Biometry, Hanover (Germany)

    2010-05-15

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter {sup 211}At and compared survival of leukaemic HL-60 and K-562 cells treated with the {sup 211}At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free {sup 211}At. The mean labelling ratio of {sup 211}At-labelled antibodies was 1:1,090 {+-} 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of {sup 211}At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. {sup 211}At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after {sup 211}At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that {sup 211}At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase {sup 211}At-anti-CD33 therapeutic effects. (orig.)

  17. Feverfew: weeding out the root of leukaemia.

    Science.gov (United States)

    Guzman, Monica L; Jordan, Craig T

    2005-09-01

    Malignant stem cells are central to the pathogenesis and perpetuation of acute myelogenous leukaemia (AML). Despite their crucial role, standard chemotherapy often does not target these critical cells and, thus, the 'root' of leukaemic disease is not eradicated. To derive better therapies, unique molecular features of malignant stem cells have been characterised for AML and evaluated with regard to ablation of disease. In the course of such studies, the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukaemia. In this article, characteristics of parthenolide are reviewed.

  18. Serum & cerebrospinal fluid ferritin levels in children with acute leukaemia.

    Science.gov (United States)

    Srinivasan, A; Rusia, U; Anand, N K; Sood, S K

    1989-06-01

    Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.

  19. Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of (/sup 3/H)serotonin

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    Tamir, H. (New York Psychiatric Inst., New York); Theoharides, T.C.; Gershon, M.D.; Askenase, P.W.

    1982-06-01

    The binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells was studied. Two types of serotonin binding protein in RBL cells was found. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 x 10/sup -6/ M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD/sub 1/ = 4.5 x 10/sup -/8 M; KD/sub 2/ = 3.9 x 10/sup -6/ M) did not bind to Con A. Moreover, binding of (/sup 3/H)serotonin to protein of Peak I was sensitive to inhibition by reserpine, while binding of (/sup 3/H)serotonin to protein of Peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract Peak I than Peak II protein. Electron microscope radioautographic analysis of the intracellular distribution of (/sup 3/H) serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules.No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but Peak I protein may be associated with the granular membrane while Peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.

  20. Enhancement of basophil apoptosis by olopatadine and theophylline.

    Science.gov (United States)

    Kawakami, Ayako; Suzukawa, Maho; Koketsu, Rikiya; Komiya, Akiko; Ohta, Ken; Yamamoto, Kazuhiko; Yamaguchi, Masao

    2008-01-01

    Regulation of basophil survival is an important aspect in the pathogenesis of allergic inflammation associated with local accumulation of basophils. However, pharmacologic modulation of basophil survival is largely unknown except for the apoptosis-enhancing effect of glucocorticoids. We tested the effects of two anti-allergic and anti-asthmatic drugs, olopatadine and theophylline, on basophil survival. Basophils were highly purified from normal human peripheral blood. Apoptosis was analyzed by flow cytometry using annexin V staining or another staining method that detected alterations in the mitochondrial transmembrane potential. In addition to the conventional method using annexin V, basophil apoptosis was successfully established by analysis of the mitochondrial transmembrane potential. Olopatadine decreased the number of live basophils, and they induced apoptosis of basophils during culture. The decline in live basophils was induced by olopatadine even when low doses of IL-3 were included in the culture medium. Theophylline also affected basophil apoptosis and induced a decrease in the number of live basophils. Basophil apoptosis was enhanced by both olopatadine and theophylline. This effect may partly explain the pharmacologic basis of why these drugs are effective on allergic diseases.

  1. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael;

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified...

  2. Mx1 GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies.

    Science.gov (United States)

    Engelhardt, Othmar G; Sirma, Hüseyin; Pandolfi, Pier-Paolo; Haller, Otto

    2004-08-01

    The interferon-induced murine Mx1 GTPase is a nuclear protein. It specifically inhibits influenza A viruses at the step of primary transcription, a process known to occur in the nucleus of infected cells. However, the exact mechanism of inhibition is still poorly understood. The Mx1 GTPase has previously been shown to accumulate in distinct nuclear dots that are spatially associated with promyelocytic leukaemia protein (PML) nuclear bodies (NBs), but the significance of this association is not known. Here it is reported that, in cells lacking PML and, as a consequence, PML NBs, Mx1 still formed nuclear dots. These dots were indistinguishable from the dots observed in wild-type cells, indicating that intact PML NBs are not required for Mx1 dot formation. Furthermore, Mx1 retained its antiviral activity against influenza A virus in these PML-deficient cells, which were fully permissive for influenza A virus. Nuclear Mx proteins from other species showed a similar subnuclear distribution. This was also the case for the human MxA GTPase when this otherwise cytoplasmic protein was translocated into the nucleus by virtue of a foreign nuclear localization signal. Human MxA and mouse Mx1 do not interact or form heterooligomers. Yet, they co-localized to a large degree when co-expressed in the nucleus. Taken together, these findings suggest that Mx1 dots represent distinct nuclear domains ('Mx nuclear domains') that are frequently associated with, but functionally independent of, PML NBs.

  3. Assessment in vitro of the genotoxicity, antigenotoxicity and antioxidant of Ceratonia siliqua L. extracts in murine leukaemia cells L1210 by comet assay.

    Science.gov (United States)

    Sassi, Aïcha; Bouhlel, Ines; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaabane, Fadwa; Ghedira, Kamel; Chekir-Ghedira, Leila

    2016-06-01

    Genotoxicity of Ceratonia siliqua extracts, was investigated by assessing their capacity to induce nucleus DNA degradation of murine leukaemia cells L1210, using the "Comet assay". The ability of total oligomer flavonoids (TOF) and aqueous extracts to protect cell DNA against oxidative stress induced by H2O2, was performed by pre- co or post-treatment of cells with the before mentioned extracts for different periods preceding exposure to H2O2 stress. No significant genotoxic effect was detected at different exposure times, except at the lowest concentration of TOF extract (16.25 μg/ml). It appears that extracts decreased DNA damage, induced by H2O2. Both of TOF and aqueous extracts exhibited cellular antioxidant capacity, with EC50 values of respectively <16.25 and < 35 μg/ml, as well as, a protective capacity against lipidperoxidation inducing using L1210 cells line as a cellular model. MDA inhibition percentages reached 88.43% and 90.52% with respectively 35.5 μg/ml of TOF extract and 70 μg/ml of aqueous extract. Antioxidant properties of carob leaf extracts revealed by our study make a good antioxidant protection and thus a good candidate as food addition component.

  4. Membrane sialic acid influences basophil histamine release by interfering with calcium dependence

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Skov, P S

    1987-01-01

    The influence of the cell membrane content of sialic acid on basophil histamine release was examined in vitro in allergic patients and normal controls. Enzymatical removal of sialic acid enhanced histamine release induced by allergen and anti-IgE, whereas an increase in membrane sialic acid content....... This difference, together with the previous finding that alterations in membrane sialic acid content is reflected in the cell sensitivity to extracellular calcium, suggest an interaction between membrane sialic acid and the calcium channels involved in basophil histamine release....

  5. Expression of the Transcription Factor E4BP4 in Human Basophils

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Gohr, Maria; Poulsen, Lars Kærgaard

    2014-01-01

    by ECL stain and X-ray film exposure. Protein band intensities were correlated to -actin expression. Results We analyzed basophils from 14 donors and found E4BP4 mRNA expression in all donors (2.33 ± 2.42) despite a low basophil RNA level. Seven donors were also tested for E4BP4 protein expression...... by Alcian blue. RNA was extracted (0.005-0.02 µg RNA from 0.5 - 1 x 106 cells), and the corresponding cDNA analyzed by real-time PCR where E4BP4 expression was calculated as 2-(CT(E4BP4) - CT(β-actin)). E4BP4 protein expression was visualized in basophil lysates (107 cells/ml) by Western blot followed...

  6. Diagnostic tests based on human basophils

    DEFF Research Database (Denmark)

    Kleine-Tebbe, Jörg; Erdmann, Stephan; Knol, Edward F;

    2006-01-01

    -maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests...

  7. Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species.

    Science.gov (United States)

    Wei, Chunmei; Xiao, Qing; Kuang, Xingyi; Zhang, Tao; Yang, Zesong; Wang, Li

    2015-11-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and a high risk of progression to acute myeloid leukaemia (AML). Fucoidan, a complex sulphated polysaccharide isolated from the cell wall of brown seaweeds, has recently attracted attention for its multiple biological activities and its potential as a novel candidate for cancer therapy. In the present study, the anti‑cancer activity of fucoidan was investigated in the MDS/AML cell line SKM‑1. Fucoidan inhibited proliferation, induced apoptosis and caused G1-phase arrest of the cell cycle in SKM‑1 cells as determined by a cell counting kit 8 assay and flow cytometry. Furthermore, reverse transcription quantitative polymerase chain reaction and western blot analyses indicated that treatment with fucoidan (100 µg/ml for 48 h) activated Fas and caspase‑8 in SKM‑1 cells, which are critical for the extrinsic apoptotic pathway; furthermore, caspase‑9 was activated via decreases in phosphoinositide-3 kinase/Akt signaling as indicated by reduced levels of phosphorylated Akt, suggesting the involvement of the intrinsic apoptotic pathway. In addition, fucoidan treatment of SKM‑1 cells resulted in the generation of reactive oxygen species (ROS) as determined by staining with dichloro-dihydro-fluorescein diacetate. These results suggested that the mechanisms of the anti‑cancer effects of fucoidan in SKM‑1 are closely associated with cell cycle arrest and apoptotic cell death, which partly attributed to the activation of apoptotic pathways and accumulation of intracellular ROS. Our results demonstrated that Fucoidan inhibits proliferation and induces the apoptosis of SKM‑1 cells, which provides substantial therapeutic potential for MDS treatment.

  8. Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells.

    Science.gov (United States)

    Chen, Yi-Chuan; Chang, Heng-Yuan; Deng, Jeng-Shyan; Chen, Jian-Jung; Huang, Shyh-Shyun; Lin, I-Hsin; Kuo, Wan-Lin; Chao, Wei; Huang, Guan-Jhong

    2013-01-01

    Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.

  9. Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia

    Science.gov (United States)

    Senda, Miho; Fukuyama, Ryuichi; Nagasaka, Tetsuro

    2016-01-01

    Aims To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis. Methods We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group. Results We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients. Conclusions These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT. PMID:26951084

  10. Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.

    Science.gov (United States)

    Matsuoka, Kunie; Shitara, Hiroshi; Taya, Choji; Kohno, Kenji; Kikkawa, Yoshiaki; Yonekawa, Hiromichi

    2013-01-01

    Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.

  11. Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.

    Directory of Open Access Journals (Sweden)

    Kunie Matsuoka

    Full Text Available Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI, a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.

  12. Surface membrane traffic in guinea pig basophils exposed to cationic ferritin.

    Science.gov (United States)

    Dvorak, A M; Dvorak, H F; Galli, S J

    1985-01-01

    Surface membrane traffic patterns can be influenced by a number of factors, including the functional state of the cell. We used transmission electron microscopy to investigate the fate of surface membrane in guinea pig basophils exposed to cationized ferritin (CF) in vitro. CF bound to the plasma membrane and was internalized on the membranes of vesicles and vacuoles, a process that was particularly prominent at the uropod of basophils exhibiting a polarized ('motile') configuration. The vesicles/vacuoles moved to the Golgi area, or, in the case of degranulating basophils, were observed in continuity with the degranulation sac, a structure formed largely by the fusion of individual cytoplasmic granule membranes. However, CF-positive vesicles were never observed to fuse directly with the membranes of intact cytoplasmic granules.

  13. 6-C-methyl flavonoids isolated from Pinus densata inhibit the proliferation and promote the apoptosis of the HL-60 human promyelocytic leukaemia cell line.

    Science.gov (United States)

    Yue, Rongcai; Li, Bo; Shen, Yunheng; Zeng, Huawu; Li, Bo; Yuan, Hu; He, Yiren; Shan, Lei; Zhang, Weidong

    2013-08-01

    Three structurally related 6-C-methyl flavonoids isolated from Pinus densata, including 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4'-trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4'-trihydroxy-3-methoxy-6-C-methylflavone (PD3), were tested for their ability to inhibit the proliferation and promote the apoptosis of the HL-60 human leukaemia cell line. Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4'-Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60 cells in a dose-dependent manner with an IC₅₀ of 7.91 µM (48 h treatment). Furthermore, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis was associated with mitochondrial membrane disruption and cytochome c release. Flow cytometry analyses revealed an increase in the hypodiploid population in 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment with a concentration of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3 inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed the cytotoxic effects of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL-60 cells. These data demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone effectively induced the apoptosis of HL-60 cells and exhibited significant anticancer activity via the mitochondrial caspase-3-dependent apoptosis pathway.

  14. Human blood basophils display a unique phenotype including activation linked membrane structures.

    Science.gov (United States)

    Stain, C; Stockinger, H; Scharf, M; Jäger, U; Gössinger, H; Lechner, K; Bettelheim, P

    1987-12-01

    To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.

  15. Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.

    Science.gov (United States)

    Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

    2015-02-01

    The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (≥50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI) = 0.09-0.79) and overall survival 78 % (95 % CI = 0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol.

  16. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial.

    Science.gov (United States)

    Chihara, Dai; Kantarjian, Hagop; O'Brien, Susan; Jorgensen, Jeffrey; Pierce, Sherry; Faderl, Stefan; Ferrajoli, Alessandra; Poku, Rebecca; Jain, Preetesh; Thompson, Phillip; Brandt, Mark; Luthra, Rajyalakshmi; Burger, Jan; Keating, Michael; Ravandi, Farhad

    2016-09-01

    Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

  17. Identification and phylogenetic characterization of a human T-cell leukaemia virus type I isolate from a native inhabitant (Rapa Nui) of Easter Island.

    Science.gov (United States)

    Ohkura, S; Yamashita, M; Cartier, L; Tanabe, D G; Hayami, M; Sonoda, S; Tajima, K

    1999-08-01

    Human T-cell leukaemia virus type I (HTLV-I) is endemic in Melanesia, one of the three ethnogeographic regions of the Pacific; in the other two regions, Polynesia and Micronesia, the incidence of the virus is relatively low. In an effort to gain new insights into the prevalence of HTLV-I in the Pacific region, we did a seroepidemiological survey on Easter Island, which is located on the eastern edge of Polynesia. Of 138 subjects surveyed, including 108 Rapa Nui (the native inhabitants of this island), we identified one HTLV-I-seropositive Rapa Nui. The new HTLV-I isolate derived from this carrier (E-12) was phylogenetically analysed to ascertain the origin and past dissemination of HTLV-I in the island. The analysis demonstrated that isolate E-12 belongs to subgroup A of the Cosmopolitan group, and that it differs from HTLV-Is found in Melanesia, which are highly divergent variants. In subgroup A, E-12 grouped with South American HTLV-Is including those from Amerindians. This result suggests that this isolate originated in South America rather than in Melanesia.

  18. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology

    Science.gov (United States)

    Hungate, Eric A.; Vora, Sapana R.; Gamazon, Eric R.; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J.; Pui, Ching-Hon; Cox, Nancy J.; Loh, Mignon L.; Yang, Jun J.; Skol, Andrew D.; Onel, Kenan

    2016-01-01

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10−15, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology. PMID:26868379

  19. Elevated Toll-Like Receptor-Induced CXCL8 Secretion in Human Blood Basophils from Allergic Donors Is Independent of Toll-Like Receptor Expression Levels.

    Directory of Open Access Journals (Sweden)

    Markus Steiner

    Full Text Available Human blood basophils have recently gained interest in addition to their function as allergic effector cells. Previous work suggests the involvement of innate immune mechanisms in the development and exacerbation of allergic responses, which might be mediated by basophils. We assayed the expression levels of Toll-like receptor (TLR 1, 2, 4 and 6 on purified basophils from birch pollen-, house dust mite-, and non-allergic individuals. Additionally, we compared cytokine and chemokine secretion upon TLR stimulation in these basophil donor groups. Expression of TLR4 on the basophils of the allergic donor groups was decreased and CXCL8 secretion was elevated upon stimulation of TLR1/2 and TLR2/6 compared to the non-allergic donors. Decreased TLR expression and elevated CXCL8 secretion may represent possible mechanisms for aggravation of allergic symptoms in case of parasitic infection.

  20. Assessment of expression of selected Bcl-2 family proteins in lymphoid infiltration in patients with B-cell chronic lymphocytic leukaemia treated with nucleoside analogues.

    Directory of Open Access Journals (Sweden)

    Janusz Kłoczko

    2008-12-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL is characterized by clonal growth and accumulation of mature lymphoid cells due to disturbance in genetically regulated form of cell death called apoptosis. The intrinsic mechanism of apoptosis is controlled by Bcl-2 family proteins. Purine nucleoside analogues induce the apoptosis in cells in a state of quiescence. The aim of the study was to assess expression of selected Bcl-2 family proteins in neoplastic infiltration in bone marrow in patients with B-CLL treated with nucleoside analogues. The study comprised examination of bone marrow obtained routinely by trephine biopsy from 18 patients with B-CLL diagnosed before administration of purine nucleoside analogues treatment and after its completion. Expression of Bcl-2, Bcl-x and Bax proteins was examined. Lymphoid cells in bone marrow were present in all patients before administration of treatment. After treatment in two patients bone marrow was infiltrated in diffuse pattern, whereas other patients presented nodular pattern of infiltration. The difference between stage of infiltration before and after treatment was statistically significant (p<0.002. High percentage of infiltration cells with positive anti Bcl-2 reaction from 42.0% in one patient to 85.33+/-3.06% in four patients before treatment was observed. After treatment percentage of infiltration cells with positive anti Bcl-2 antibody reaction was from 33.0+/-18.38% in two patients to 99.0% in one patient. Positive correlation between stage of infiltration and expression of Bcl-2 protein was confirmed before and after treatment. Such correlations were not observed in case of Bax and Bcl-x. Strong staining of immunohistochemical reaction of cells in lymphoid infiltration with Bcl-2 antibody was confirmed. There was a difference between Bcl-/Bax ratio before and after treatment. Immunohistochemical assessment of expression of Bcl-2 family proteins in cells of lymphoid infiltration in bone

  1. Some invariant properties of IgE-mediated basophil activation and desensitization

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, B.; Dembo, M.; Sobotka, A.K.; Lichtenstein, L.M.

    1979-10-01

    We investigate certain general properties of antigen induced degranulation of sensitized basophils by analyzing two types of experiments: experiments in which we expose basophils to two antigens seuquentially and then determine the fraction of histamine released; and experiments in which we obtain time-dependent release and desensitization curves. To analyze the latter type of experiments we introduce a new way to plot release and desensitization data that depends on the nature of the interactions of histamine-containing units (histamine quanta) with themselves or the cells degranulation apparatus, but not on any specific properties of the antigen. From our analysis we conclude that: (1) a fraction of histamine within a population of basophils is nonreleasable by antigenic stimulation. (2) When a basophil degranulates the initial release of histamine appears to inhibit subsequent release. (3) The rate of histamine release is proportional to the amount of releasable histamine remaining in the cells when the amount remaining is small, as expected if release of histamine granules is a stochastic process. (4) There is no dependence of desensitization on the extracellular calcium concentration.

  2. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia : a time-dependent analysis

    NARCIS (Netherlands)

    Versluis, Jurjen; Hazenberg, Carin L. E.; Passweg, Jakob R.; van Putten, Wim L. J.; Maertens, Johan; Biemond, Bart J.; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C.; Pabst, Thomas; Lowenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J.

    2015-01-01

    Background Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effecti

  3. Ultrastructural localization of Charcot-Leyden crystal protein in human eosinophils and basophils.

    Science.gov (United States)

    Calafat, J; Janssen, H; Knol, E F; Weller, P F; Egesten, A

    1997-01-01

    The Charcot-Leyden crystal (CLC) protein with lysophospholipase activity and carbohydrate-binding properties is a characteristic constituent of eosinophils and basophils. We investigated its subcellular distribution using immunoelectron microscopy. Eosinophil progenitors, mature eosinophils and basophils all contained CLC protein in their cytosol and in the euchromatin of the nucleus. A minor population of granules in eosinophils, increasing in number with maturation, and a more abundant granule-population in basophils, were found to contain CLC protein. Double-labeling experiments showed, in eosinophils, that CLC protein-containing granules contain also eosinophil peroxidase, a characteristic specific granule protein. This suggests a relationship between the CLC protein-containing organelle and the specific granule. In basophils both the CLC protein positive and the negative granules showed the same characteristic particulate-like structure of the granular matrix and both share the same membrane marker CD63. In nasal polyps, macrophages were observed phagocytosing necrotic eosinophils. In these macrophages CLC protein-containing vesicles were observed, probably representing late endosomes. The dual (cytosolic/nuclear and granular) localization of CLC protein suggests that this protein enters both a secretory and a nonsecretory pathway during its biosynthesis, indicating functional roles for this protein both within the cell and extracellularly.

  4. Acute leukaemia following renal transplantation.

    Science.gov (United States)

    Subar, M; Gucalp, R; Benstein, J; Williams, G; Wiernik, P H

    1996-03-01

    Four renal transplant patients on immunosuppressive therapy who presented with acute myeloid leukaemia are described. In two cases, azathioprine may have played an important role as a cofactor in leukaemogenesis. In a third case, the alkylating agent cyclophosphamide may have contributed. All patients were treated for leukaemia with full doses of cytotoxic chemotherapy and, in each case, a functioning renal allograft was preserved throughout the treatment despite attenuation of immunosuppressive therapy. Three patients achieved complete remission. Of the three, one is surviving at 2 years and two expired during the pancytopenic phase of their treatment with no active leukaemia present, and with intact renal function. As increasing expertise in the field of organ transplantation allows patients to survive longer, such patients' exposure to immunosuppressive and potentially leukaemogenic drugs is prolonged. The risk of secondary neoplasia has been previously documented in this population. Two of the four cases reported here suffered from polycystic kidney disease as their underlying condition. While this report suggests that the leukaemias are related to renal transplantation, we cannot rule out an association with the underlying disease which led to the transplant. This report further suggests that the leukaemia that develops in such patients may respond to standard therapy, and that such treatment does not compromise the transplanted kidney.

  5. Pros and Cons of Clinical Basophil Testing (BAT)

    NARCIS (Netherlands)

    Hoffmann, Hans Jürgen; Knol, Edward F; Ferrer, Martha; Mayorga, Lina; Sabato, Vito; Santos, Alexandra F; Eberlein, Bernadette; Nopp, Anna; MacGlashan, Donald

    2016-01-01

    PURPOSE OF REVIEW: We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages. RECENT FINDINGS: There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to

  6. Grape seed proanthocyanidin extract induced mitochondria-associated apoptosis in human acute myeloid leukaemia 14.3D10 cells

    Institute of Scientific and Technical Information of China (English)

    HU Hong; QIN Yi-min

    2006-01-01

    @@ The important aim in cancer treatment is the selective killing of cancer cells without damaging healthy cells and the most commonly used chemotherapy for eliminating cancer is achieved by activating the mitochondrial apoptotic pathway.1 Therefore, identification of new agents that can selectively kill cancer cells becomes crucial in cancer clinical treatment.

  7. Childhood leukaemia in the Netherlands : a register based epidemiologic study

    NARCIS (Netherlands)

    H.A. Moll (Henriëtte)

    1983-01-01

    textabstractLeukaemia, literally "white blood", is the most common type of malignancy in childhood (Birch et al., 1980). The clinical features are caused by abnormal proliferation of one or more of the blood-forming cellular elements. The immature malignant cells usually disturb normal haematopoiesi

  8. Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets

    Directory of Open Access Journals (Sweden)

    Chirumbolo Salvatore

    2010-09-01

    Full Text Available Abstract Background Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release. Results Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism. Conclusions These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.

  9. The effect of specific immunotherapy on NK cell activity and the expression of basophil in children with asthma%特异性免疫治疗哮喘患儿NK细胞活性和嗜碱性细胞表达变化的影响

    Institute of Scientific and Technical Information of China (English)

    张慧娟; 董一慧; 袁显文

    2016-01-01

    目的 探讨特异性免疫治疗哮喘患儿自然杀伤细胞(natural killer cell,NK)活性和嗜碱性细胞表达变化的影响.方法 回顾性分析本院2012年12月至2014年12月收治的97例哮喘息儿的临床资料,按照治疗方法分为对照组(47例)和观察组(50例),分别给予常规治疗和特异性免疫治疗.观察两组的NK细胞活性和嗜碱性细胞表达变化,并进行比较.结果 治疗前,两组患者的NK细胞活性与嗜碱性细胞表达水平经比较差异无统计学意义(P<0.05);经过不同的治疗之后,观察组和对照组的NK细胞活性分别为(12.12±1.51)%、(10.10±2.10)%,较之本组治疗前均得到显著的提高(P<0.05);治疗后两组比较差异有统计学意义(P<0.05).观察组和对照组的嗜碱性细胞表达水平分别为(0.41±0.11)%、(0.51±0.15)%,较之本组治疗前均得到显著的下降(P<0.05);治疗后两组比较差异有统计学意义(P<0.05).结论 特异性免疫治疗哮喘患儿可以显著增强其NK细胞活性,并降低嗜碱性细胞的表达水平.%Objective To investigate the effect of specific immunotherapy on natural killer cell (NK cell) activity and the expression of basophil in asthmatic children.Methods A retrospective analysis was performed on clinical data of 97 children with asthma in our hospital from December 2013 to December 2014,and they were divided into control group (47 cases) and observation group (50 cases) according to treatment methods,and were given conventional therapy and specific immunotherapy respectively.The changes of NK cell activity and the expression of basophil in two groups were observed and compared.Results Before treatment,there were no statistically significant differences in NK cell activity and the expression of basophil between two groups (P>0.05);after treatment,NK cell activity in observation group and control group were (12.12±1.51)% and (10.10±2.10)% respectively,improved significantly compared

  10. Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1.

    Science.gov (United States)

    Salah, R; Michaud, P; Mati, F; Harrat, Z; Lounici, H; Abdi, N; Drouiche, N; Mameri, N

    2013-01-01

    In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight-activity relationship and an electrostatic interaction-activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

  11. Acute T-cell lymphoblastic leukaemia presenting with cutaneous involvement in a child: a rare case report

    Directory of Open Access Journals (Sweden)

    Lohit Kumar Kalita

    2015-05-01

    Full Text Available Primary cutaneous involvement in T-cell lymphoblastic leukemia is rare in childhood. We present a case of 6-year-old girl admitted to our hospital because of multiple skin lesions. She was looked pale and weak. Generalized lymphadenopathy was present. Complete blood count revealed 216,000/mm3 white blood cell count. Peripheral blood smear showed 80% lymphoblasts. Bone marrow aspiration revealed 96% blastic cells with immunophenotype and morphological characteristics of acute lymphoblastic leukemia (T-ALL which was confirmed by flowcytometry. ALL BFM -95 remission induction treatment protocol was started. Skin lesion remained same after two month of the cytotoxic therapy. The symptoms became more aggressive and she died after 4 months of treatment. [Int J Res Med Sci 2015; 3(5.000: 1285-1287

  12. Control of feline leukaemia virus.

    NARCIS (Netherlands)

    K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1989-01-01

    textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (

  13. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian

    2013-01-01

    secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single m...

  14. Basophilic deposits on the cupula: preliminary findings describing the problems involved in studies regarding the incidence of basophilic deposits on the cupula.

    Science.gov (United States)

    Naganuma, H; Kohut, R I; Ryu, J H; Tokumasu, K; Okamoto, M; Fujino, A; Hoshino, I; Arai, M

    1996-01-01

    In this study, the possibility of whether basophilic deposits adhered to the cupulas in the semicircular canals was investigated histologically. Results indicated that basophilic deposits were present in all three cupulas of the semicircular canals. The overall incidence of basophilic deposits in the superior, lateral and posterior semicircular canal cupulas was 26%, 41% and 37%, respectively. The incidence of basophilic deposits bound to the cupulas increased with age. The possible origin of these basophilic deposits on the cupulas and the increased incidence of basophilic deposits with increasing age are discussed.

  15. Relapsed/refractory paediatric T cell lymphoblastic leukaemia and lymphoma. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available IA. A.3.2Name or abbreviated title of the trial where available NK cells in leukemia / lymphoma Células NK en leucemia...a de rescate en pacientes con leucemia aguda linfoblástica/linfoma linfoblástico (LLT) en recaída o refracta...HIV serology 1. Pacientes de edad comprendida entre 0 y 21 años diagnosticados de leucemia aguda linfoblásti

  16. Signaling transduction pathways involved in basophil adhesion and histamine release

    DEFF Research Database (Denmark)

    Sha, Quan; Poulsen, Lars K.; Gerwien, Jens

    2006-01-01

    Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles ...... of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR)....

  17. The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells

    OpenAIRE

    2012-01-01

    Abstract Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn++-chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, wh...

  18. Inhibition by adenosine of histamine and leukotriene release from human basophils.

    Science.gov (United States)

    Peachell, P T; Lichtenstein, L M; Schleimer, R P

    1989-06-01

    Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immunologically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine greater than or equal to N-ethylcarboxamidoadenosine (NECA) greater than adenosine greater than or equal to R-phenylisopropyladenosine (R-PIA) greater than or equal to S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipyridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).

  19. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding

    Science.gov (United States)

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G.

    2016-01-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses. PMID:27708445

  20. The expression of CD123 can decrease with basophil activation: implications for the gating strategy of the basophil activation test

    OpenAIRE

    Santos, Alexandra F.; Bécares, Natalia; Stephens, Alick; Turcanu, Victor; Lack, Gideon

    2016-01-01

    Background Basophil activation test (BAT) reproduces IgE-mediated allergic reactions in vitro and has been used as a diagnostic test. Different markers can be used to identify basophils in whole blood and have implications for the outcome of the test. We aimed to assess changes in the expression of CD123 and HLA-DR following basophil activation and to select the best gating strategy for BAT using these markers. Methods BAT was performed in whole blood from 116 children. Peanut extract, anti-I...

  1. Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2

    Directory of Open Access Journals (Sweden)

    Sanja Perkovic

    2012-09-01

    Full Text Available Aggressive natural killer-cell leukaemia (ANKL is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV and P-glycoprotein (P-gp expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56+ NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2 MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

  2. Lack of expression of the chondroitin sulphate proteoglycan neuron-glial antigen 2 on candidate stem cell populations in paediatric acute myeloid leukaemia/abn(11q23) and acute lymphoblastic leukaemia/t(4;11)

    NARCIS (Netherlands)

    J. Neudenberger (J.); M. Hotfilder (Marc); A. Rosemann (Annegret); C. Langebrake (C.); D. Reinhardt (Dirk); R. Pieters (Rob); A. Schrauder (André); M. Schrappe (Martin); S. Röttgers (Silja); J. Harbott (Jochen); J. Vormoor (Josef)

    2006-01-01

    textabstractIt has increasingly been acknowledged that only a few leukaemic cells possess the capability to renew themselves and that only these self-renewing leukaemic stem cells are able to initiate relapses. Therefore, these leukaemic stem cells should be the target cells for therapy and for mini

  3. Analysis of atypical lymphocyte and basophilic granulocyte warning information indicated by Sysmex XE-5000 blood cell analyzer%Sysmex XE-5000血细胞分析仪对异型淋巴细胞和嗜碱性粒细胞的报警提示分析

    Institute of Scientific and Technical Information of China (English)

    王凤; 刘爽; 万丽平; 韩晓丹; 王贞

    2015-01-01

    目的:评价Sysmex XE-5000血细胞分析仪对异型淋巴细胞和嗜碱性粒细胞的报警提示功能。方法收集Sysmex XE-5000血细胞分析仪同时提示异型淋巴细胞和嗜碱性粒细胞的外周血标本197份,以及单独提示异型淋巴细胞的外周血标本914份,进行显微镜复检,以核实报警提示信息是否正确。结果以显微镜复检结果为金标准,同时提示异型淋巴细胞和嗜碱性粒细胞增多的标本经复检后嗜碱性粒细胞在正常范围内,异型淋巴细胞检出的符合率为64.9%;单独提示异型淋巴增多的标本经复检后符合率为72.5%,前者明显低于后者,差异有统计学意义(P<0.05)。结论 Sysmex XE-5000血细胞分析仪同时报警提示异型淋巴细胞和嗜碱性粒细胞增多时,两者计数有一定相互干扰,需结合显微镜复检,以降低漏诊和误诊概率。%Objective To evaluate the performance of the Sysmex XE-5000 analyzer for analyzing atypical lymphocytes ,baso-philic granulocytes and their abnormalities warnings .Methods A total of 197 specimens with both atypical lymphocytes and baso-philic granulocytes warnings and 914 specimens with single warning of atypical lymphocytes indicated by Sysmex-5000 blood cell analyzer were collected and inspected by microscope simultaneously .Results Using microscopic examination as a standard ,baso-philic granulocytes within the normal range ,the coincidence rate of samples with both atypical lymphocytes and basophilic granulo-cytes warnings was 64 .9% ,while the coincidence rate of samples with single warning of atypical lymphocytes was 72 .5% .The for-mer was significantly lower than the latter(P<0 .05) .Conclusion When Sysmex XE-5000 indicates atypical lymphocytes and baso-philic granulocytes simultaneously ,there is interference between each other .It should be combined with microscopic examination in order to reduce the probability of missed diagnosis and

  4. [Human basophil degranulation test. Results of a modified technic (I)].

    Science.gov (United States)

    Román Pérez, F; Berlanga Cortés, J A; Urquiă, M; Guerra Pasadas, F; Peña Martínez, J

    1986-01-01

    The degranulation of human basophils towards antigenic substances, to which they must be previously sensitized as a result of the antigen-antibody union at the membrane level, is a phenomenon that has an important application complementing diagnosis of diseases mediated by the Gell and Coombs classification of Type I Hypersensitivity, on which the principle of Human Basophils Degranulation Test (HBDT) was based. An essential requirement is to be able to collect an adequate quantity of basophils, as well as the visualization by means of a technique of convenient stain. In this work, we show a modified HBDT technique for basophil granulocytes staining. A total of 33 HBDT was carried out on patients sensitive to grass pollen and/or Olea europea pollen and/or D. pteronyssinus, and as controls, HBDT was done on healthy individuals with negative clinical history. Basophil enrichemnt from the circulating blood sample was done by means of centrifugation in Percoll density gradients of 1072, 1076, 1080 and 1082, and we obtained a higher number of basophils with a density of 1080 at 400 Xg for 30 minutes. The cellular bottom was resuspended in 600 microliters of PBS. We employed lyophilized antigenic extracts from grass pollen, Olea europea and D. pteronyssinus, employing weight/volume concentration of 10(-4), 10(-5), 10(-6) and 10(-7). The optimum dilutions were 10(-5) for grass pollen and D. pteronyssinus.

  5. Epidural spinal cord compression as initial clinical presentation of an acute myeloid leukaemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Dominique N'Dri Oka; Alpha Boubacar Bah; André Valentin Tokpa; Louis Derou

    2016-01-01

    Epidural localization of myeloid leukaemia is rarely reported.Spinal cord compression as an initial presentation of acute myeloid leukaemia is extremely rare.This is a report of a 17-year-old black boy who presented to emergency department with neurological symptoms of spinal cord compression.Imaging modalities showed multiple soft tissue masses in the epidural space.After surgical treatment,histopathological examination of the epidural mass showed myeloid leukaemia cells infiltration.Literature review on Medline and "scholar Google" database was done.The characteristics and management of extra-medullary leukaemia are discussed.Granulocytic sarcoma,myeloid sarcoma or chloroma with acute myeloid leukaemia should be considered as part of epidural spinal cord compression.Therefore surgery is indicated on an emergent basis.

  6. Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj;

    2006-01-01

    Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells...

  7. Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker

    NARCIS (Netherlands)

    Bellou, A.; Saint-Laudy, J.; Knippels, L.; Montémont, C.; Vauthier, E.; Gerard, P.; Pellegrom, H.; Koerkamp, E.K.; Lesesve, J.F.; Guéant, J.L.; Lambert, H.; Mallié, J.P.

    2003-01-01

    Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether seru

  8. Immunophenotypic and DNA genotypic analysis of T-cell and NK-cell subpopulations in patients with B-cell chronic lymphocytic leukaemia (B-CLL).

    Science.gov (United States)

    Frolova, E A; Richards, S J; Jones, R A; Rawstron, A; Master, P S; Teasdale, J; Short, M; Jack, A S; Scott, C S

    1995-01-01

    Absolute numbers and distributions of peripheral blood T-cells and NK cells were immunophenotypically determined in 21 patients with B-CLL and compared with those obtained from a series of 13 elderly normal controls with an age range of 60-87 years. For absolute CD3+, CD4+ and CD8+ T-cell, and CD16+ NK subpopulation numbers, there were no consistent differences between the normal and B-CLL groups although some individual patient variation was seen. Immunophenotypic analyses did however reveal that CD3+ T-cells in almost half (10/21) of the B-CLL patients were Ia+ (defined as > 20% positive cells), compared to 0/13 of the elderly control group (p 20%) proportions of CD3+ T-cells co-expressing Ia further showed that CD45RO expression by CD4+ fractions was particularly prominent in the Ia+ subgroup, and that the relative increase of CD4+CD45RO+ cells was primarily a consequence of decreased absolute numbers of CD4+CD45RA+ lymphocytes. This study also examined extracted DNA from enriched CD3+ T-cell fractions (obtained by immunomagnetic bead selection in 9 of the B-CLL cases) by PCR analysis with two primers for the T-cell gamma gene locus. With the V gamma C (consensus) primer, 8/9 cases were polyclonal and the remaining case was oligoclonal. For comparison, 7/9 CD3+ fractions were oligoclonal with the V gamma 9 primer with the other two cases being polyclonal. No monoclonal CD3+ components were found. It is suggested that the observed increased Ia expression by CD3+ cells and the predominance of CD4+ cells expressing membrane CD45RO in patients with B-CLL may be of potential relevance to understanding the pathogenesis and patterns of disease progression.

  9. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels

    2007-01-01

    Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1......(SETBP1) fusion signals; other analyses showed that exon 12 of NUP98 was fused in-frame with exon 5 of SETBP1. Nested polymerase chain reaction did not amplify the reciprocal SETBP1/NUP98, suggesting that NUP98/SETBP1 transcript is pathogenetically important. SETBP1 has previously not been implicated...

  10. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  11. Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression.

    Science.gov (United States)

    Pozzi, Sarah; Geroldi, Simona; Tedone, Elisabetta; Luchetti, Silvia; Grasso, Raffaella; Colombo, Nicoletta; Di Grazia, Carmen; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Van Lint, Maria Teresa; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Signori, Alessio; Bacigalupo, Andrea

    2013-02-01

    We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.

  12. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP of the European Society for Blood and Marrow Transplantation (EBMT

    Directory of Open Access Journals (Sweden)

    Xavier Poiré

    2017-01-01

    Full Text Available Abstract Background Acute myeloid leukaemia (AML with 17p abnormalities (abn(17p carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT appears as the only potential curative option. Methods To address outcomes after allo-SCT in patients with abn(17p, we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results One hundred thirty-nine patients with confirmed abn(17p have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1. Median age was 54 years old. Abn(17p was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q- in 55%, monosomy 7 (-7 in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59% had a reduced-intensity conditioning regimen. The 2-year overall survival (OS and leukaemia-free survival (LFS were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM was 15%, and 2-year relapse incidence (RI was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions In contrast to the dismal prognosis reported for AML patients harbouring abn(17p undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

  13. Influence of nimodipine, verapamil and lanthanum on histamine release from human basophils

    DEFF Research Database (Denmark)

    Jensen, C B; Thastrup, Ole; Norn, S;

    1987-01-01

    Our previous studies suggest that the membrane content of sialic acid influences histamine release from human basophils by interfering with the transmembraneous calcium fluxes preceding histamine release. In this study we investigated a possible interaction between membrane sialic acid...... and the calcium channels, using the calcium antagonists nimodipine, verapamil and lanthanum. Anti-IgE-induced histamine release was inhibited by verapamil, nimodipine and lanthanum. When cells were pretreated with sialidase in order to remove sialic acid from the cell membrane, the inhibitory action of nimodipine...

  14. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

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    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  15. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  16. Hypoxia and hypoxia-inducible factors in leukaemias

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    Margaux eDeynoux

    2016-02-01

    Full Text Available Despite huge improvements in the treatment of leukaemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukaemic stem cells (LSCs within the bone marrow, which are able to self-renew and therefore re-establish the full tumour. The marrow microenvironment contributes considerably in supporting the protection and development of leukaemic cells. LSCs share specific niches with normal haematopoietic stem cells with the niche itself being composed of a variety of cell types including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells and vascular cells. A hallmark of the haematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of HSCs. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor family. In solid tumours, it has been well-established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukaemia is not considered a solid tumour, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukaemic cell proliferation, differentiation and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumour suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukaemic development and therapeutic resistance, and to discuss the recent hypoxia-based strategies proposed to eradicate leukaemias.

  17. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P.

    Science.gov (United States)

    Zheng, Wenjiao; Wang, Junling; Zhu, Wei; Xu, Chiyan; He, Shaoheng

    2016-06-01

    Human basophils have been implicated in the pathogenesis of chronic spontaneous urticaria (CSU), and substance P (SP) is a possible candidate as histamine-releasing factor in some patients with CSU. However, little is known of relationship between basophils and SP in CSU. In the present study, we investigated expression of SP and NK1R on basophils from patients with CSU, and influence of SP on basophil functions by using flow cytometry analysis, basophil challenge, and mouse sensitization model techniques. The results showed that plasma SP level and basophil numbers in CSU patients were higher than that in HC subject. The percentages of SP+ and NK1R+ basophils were markedly elevated in CSU blood in comparison with HC blood. Once added, SP induced up to 41.2 % net histamine release from basophils of CSU patients, which was comparable with that provoked by anti-IgE, and fMLP. It appeared that SP induced dramatic increase in blood basophil numbers of mice following peritoneal injection. Ovalbumin (OVA)-sensitized mice had much more SP+ and NK1R+ basophils in blood than non-sensitized mice. In conclusion, the elevated plasma concentration of SP, upregulated expression of SP and NK1R on basophils, and the ability of SP in induction of basophil degranulation and accumulation indicate strongly that SP is most likely a potent proinflammatory mediator, which contributes greatly to the pathogenesis of CSU through basophils. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of CSU.

  18. Evaluation of Basophil Infiltration into the Skin Lesions of Tick Bites

    Directory of Open Access Journals (Sweden)

    Kyoko Nakahigashi

    2013-02-01

    Full Text Available Recently, it has been described that basophils play an essential role in antibody-mediated acquired immunity against ticks in mice. However, it is still unknown whether basophil infiltration has any significance in the infestation with ticks in humans. In this report, we have evaluated the infiltration of basophils into human skin lesions of tick bites.

  19. BMX tyrosine kinase gene is expressed in granulocytes and myeloid leukaemias.

    Science.gov (United States)

    Kaukonen, J; Lahtinen, I; Laine, S; Alitalo, K; Palotie, A

    1996-09-01

    The growth and maturation of haemopoietic cells is regulated by signal transduction through tyrosine protein kinases. Recently, a novel cytoplasmic tyrosine kinase gene in chromosome X, called Bmx, was identified in human bone marrow RNA. Bmx belongs to a subfamily of tyrosine kinases which are expressed in various haemopoietic cell lineages. We studied Bmx expression using RT-PCR of RNA from fractionated peripheral blood leucocytes, progenitor-enriched fractions of cord blood and from bone marrow or peripheral blood samples from leukaemia patients. Bmx was strongly expressed in haemopoietic tissues and enhanced in neutrophilic granulocytes. Bmx mRNA was also found in CD34-positive progenitor cells from cord blood. All samples (10/10) of patients with acute myeloid leukaemia and (4/4) with chronic myeloid leukaemia showed expression of Bmx. In contrast, none of the samples of acute lymphoid leukaemia (0/8) and only one out of six samples of chronic lymphoid leukaemia expressed Bmx. In conclusion, Bmx expression seems to be associated with myelopoiesis.

  20. Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia

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    Čolović Milica

    2011-01-01

    Full Text Available Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.

  1. Absence of activated murine leukaemia virus in X-irradiated CBA/H-T6Crc mice

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, H.C.; Tuffrey, M.; Wilson, L.; Barnes, R.D. (Medical Research Council, Harrow (UK). Clinical Research Centre)

    1981-04-01

    CBA/H-T6Crc mice, a substrain that does not normally express demonstrable levels of murine leukaemia virus (MuLV) and has a low natural incidence of leukaemia, were examined for evidence of virus activation at various times following X-irradiation. Although X-irradiation caused a high incidence of leukaemia, no ecotropic, xenotropic or recombinant MuLV was detected by in vitro co-cultivation of bone marrow, spleen and thymus cells from pre-leukaemic and leukaemic animals with selectively permissive cell lines followed by indirect immunofluorescence for MuLV group-specific (gs) antigen. These results therefore, are not consistent with the hypothesis that endogenous viruses are the universal aetiological agents of leukaemia.

  2. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael

    2002-01-01

    by the histamine content of the adhering basophils. The spontaneous adhesion to fibronectin was higher than to laminin and collagen type I. Both spontaneous adhesion to fibronectin and interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA...

  3. Importance of basophil activation testing in insect venom allergy

    Directory of Open Access Journals (Sweden)

    Kosnik Mitja

    2009-12-01

    Full Text Available Abstract Background Venom immunotherapy (VIT is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, there are still many questions and controversies regarding immunotherapy, like selection of the appropriate allergen, safety and long term efficacy. Methods Literature review was performed to address the role of basophil activation test (BAT in diagnosis of venom allergy. Results In patients with positive skin tests or specific IgE to both honeybee and wasp venom, IgE inhibition test can identify sensitizing allergen only in around 15% and basophil activation test increases the identification rate to around one third of double positive patients. BAT is also diagnostic in majority of patients with systemic reactions after insect stings and no detectable IgE. High basophil sensitivity to allergen is associated with a risk of side effects during VIT. Persistence of high basophil sensitivity also predicts a treatment failure of VIT. Conclusion BAT is a useful tool for better selection of allergen for immunotherapy, for identification of patients prone to side effects and patients who might be treatment failures. However, long term studies are needed to evaluate the accuracy of the test.

  4. Structural studies on leukaemia inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Norton, R.S.; Maurer, T.; Smith, D.K. [Biomolecular Research Institute, Parville (Australia); Nicola, N.A. [Institute of Medical Research, Melbourne (Australia)

    1994-12-01

    Leukaemia Inhibitory Factor (LIF) is a pleiotropic cytokine that acts on a wide range of target cells, including mega-karyocytes, osteoblasts, hepatocytes, adipocytes, neurons, embryonic stem cells, and primordial germ cells. Many of its activities are shared with other cytokines, particularly interleukin-6, oncostatin-M, ciliary neurotrophic factor, and granulocyte colony-stimulating factor (G-CSF). Although secreted in vivo as a glycoprotein, nonglycosylated recombinant protein expressed in E. coli is fully active and has been used in our nuclear magnetic resonance (NMR) studies of the three-dimensional structure and structure-function relationships of LIF. With 180 amino acids and a molecular mass of about 20 kDa, OF is too large for direct structure determination by two-dimensional and three-dimensional {sup 1}HNMR. It is necessary to label the protein with the stable isotopes {sup 15}N and {sup 13}C and employ heteronuclear three-dimensional NMR in order to resolve and interpret the spectral information required for three-dimensional structure determination. This work has been undertaken with both human LIF and a mouse-human chimaera that binds to the human LIF receptor with the same affinity as the human protein and yet expresses in E. coli at much higher levels. Sequence-specific resonance assignments and secondary structure elements for these proteins will be presented and progress towards determination of their three-dimensional structures described.

  5. The influence of joint application of arsenic trioxide and daunorubicin on primary acute promyelocytic leukaemia cells and apoptosis and blood coagulation of cell strain.

    Science.gov (United States)

    Zhang, Xiaojuan; Qin, Na; Chen, Xinghua; Guo, Shuxia

    2015-05-01

    This test cultivated three groups of acute promyelocytic leukemia (APL) and NB4 cells in liquid in vitro, processed them with arsenic trioxide (ATO), daunorubicin (DNR), ATO+DNR respectively, and then set up blank control group. Apoptosis of cells in each group was observed using flow cytometry, procoagulant activity of APL and NB4 cells in each group was detected with recalcification time, and expressions of tissue factor (TF), thrombomodulin and annexin II of NB4 cells in each group were measured using ELISA method. The results showed that the apoptosis rate increased 4-8 times compared with blank control group after processing APL and NB4 cells with ATO and DNR; procoagulant activity decreased obviously; and expression of TF and annexin II of NB4 cells reduced significantly (P<0.05). We concluded that combination of ATO and DNR could promote APL and NB4 cell apoptosis effectively without aggravating blood coagulation disorders, which might improve coagulation function of APL by inhibiting coagulation and hyperfibrinolysis through reducing expression of TF and annexin II. This drug combination may be a safe and effective method in the treatment of APL of primary high white blood cells type.

  6. Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker.

    Science.gov (United States)

    Bellou, A; Saint-Laudy, J; Knippels, L; Montémont, C; Vauthier, E; Gerard, P; Pellegrom, H; Koerkamp, E K; Lesesve, J F; Guéant, J L; Lambert, H; Mallié, J P

    2003-03-01

    Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether serum-specific IgE from Brown Norway (BN) rats prepared for ovalbumin (OVA)-induced anaphylactic shocks can activate human basophils which has a potential interest in experimental allergy: such a test could rapidly assert an IgE sensitization in laboratory animals genetically T-helper 2 (Th2)-predisposed. Rats (n = 39) were immunized three times (day 0, day 5 and day 21) with OVA injected subcutaneously. One week after the third immunization, a shock was induced with an intravenous (i.v.) bolus of OVA. Sensitization was assessed by passive cutaneous anaphylaxis (PCA) test and dosages of serum IgE antibodies anti-OVA by enzyme-linked immunosorbent assay. Blood basophils were counted before and during the shock. Before the shock induction (at day 21), an LHR test was performed on rat blood, and human basophils were sensitized with rat sera. HBA was demonstrated by the increase in the percentage of cells expressing CD63 antigen membrane, measured by flow cytometry. Twenty-one days after the first subcutaneous (s.c.) immunization, the rat serum induced a significant HBA. HBA was observed neither with the same serum previously heated nor with the serum from nonimmunized rats (NIRs). OVA-specific IgEs were significantly increased in immunized rat (IR) serum. The PCA test was negative when the serum was previously heated (56 degrees C). We never observed any circulating basophils, and LHR test was negative. After OVA i.v. administration, all IRs died rapidly. HBA testing strongly suggests a mediation by specific IgE in the increase of CD63 in BN rats. Thus, HBA test seems useful in assessing whether an experimental allergy was induced in animals genetically predisposed to an immune

  7. Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant

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    P. Savini

    2015-01-01

    Full Text Available Mast cell leukemia (MCL is a very rare form of systemic mastocytosis (SM with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50–60% of atypical mast cells (MCs. She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

  8. Dissecting the Entry Route of Saporin-based a-CD7 Immunotoxins in Human T-Cell Acute Lymphoblastic Leukaemia Cells

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    Maria Serena Fabbrini

    2013-01-01

    Full Text Available Elucidating the intracellular fate(s of targeted toxins is of fundamental importance for their optimal use as anticancer drugs, since the biochemical targets of their enzymatic activity reside in the cell cytoplasm, as in the case of the plant ribosome inactivating proteins (RIP saporin, ricin and of bacterial toxins. In this paper, we compared the cell surface binding and cytotoxic properties of the model RIP ricin to an immunotoxin constructed with a monoclonal antibody directed against the human T-cell marker CD7 covalently linked to saporin (CD7-SAP. Our results indicate that, despite the fact that internalization takes place via an apparently common entry route leading to the Golgi complex, surprisingly, the addition of an endoplasmic reticulum retrieval C-terminal signal (KDEL to CD7-SAP does not potentiate its cytotoxicity. In addition, while ricin toxicity is clearly reduced by Brefeldin A under conditions where this fungal metabolite causes Golgi stack disruption, we paradoxically observed a potentiating effect by Brefeldin A on CD7-SAP cytotoxicity suggesting that this inhibitor interferes with retrograde route(s other than the well established Trans-Golgi Network-ER retrograde route.

  9. Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

    DEFF Research Database (Denmark)

    Platzer, M H; Grattan, C E H; Poulsen, Lars K.

    2005-01-01

    Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immuno......Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against...... the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients...

  10. Detection of homocytotropic antibody in lambs infested with the louse, Bovicola ovis, using a basophil histamine-release assay.

    Science.gov (United States)

    Pfeffer, A; Phegan, M D; Bany, J

    1997-07-01

    The utility of a basophil histamine-release assay using washed whole blood cells was examined in lambs and was used to determine if homocytotropic antibody with specificity for Bovicola ovis was produced in response to infestation with the louse. Maximal histamine release in the assay in response to Concanavalin A, anti-ovine IgE monoclonal antibody and, in sensitized lambs, to B. ovis antigen ranged from 18 to 48%. Histamine release from blood cells in response to B. ovis antigen was significantly higher in louse-infested lambs than in louse-naive lambs and was significantly correlated with louse and cockle scores. Passive cutaneous anaphylaxis (PCA) tests were negative with sera obtained from the lambs at the same time as blood for the basophil histamine-release assay. Serum histamine levels also were significantly higher in the louse-infested lambs than in louse-naive lambs and were significantly correlated with louse and cockle scores. The present results support a role for B. ovis-specific homocytotropic antibody in the development of cockle and indicate that the basophil histamine-release assay is more sensitive than the PCA test.

  11. An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population

    NARCIS (Netherlands)

    Hesseling, PB; Buurman, M; Oud, C; Nel, ED

    1997-01-01

    The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South African between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age <2 and > 8 years, and white cell count >20 x

  12. Acute leukaemia: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Meenaghan, Teresa

    2012-01-01

    Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

  13. Short-, Intermediate-, and Long-Term Changes in Basophil Reactivity Induced by Venom Immunotherapy

    OpenAIRE

    Rodríguez Trabado, Ana; Cámara Hijón, Carmen; Ramos Cantariño, Alfonso; Romero-Chala, Silvia; García-Trujillo, José Antonio; Fernández Pereira, Luis Miguel

    2016-01-01

    Purpose The basophil activation test (BAT) has been used to monitor venom immunotherapy (VIT) due to its high specificity. A previous study has reported a good correlation between a significant decrease in basophil activation during 5 years of VIT and clinical protection assessed by sting challenge. The following prospective study was performed to examine changes in basophil reactivity over a complete VIT period of 5 years. Methods BAT in a dose-response curve was studied prospectively in 10 ...

  14. [Level of histamine in supernatants from the basophil activation test: applications to hymenoptera allergy and drug allergy--preliminary study].

    Science.gov (United States)

    Tamim, S; Lauret, M G; Drouet, M; Sabbah, A

    1999-02-01

    Histamine Release technic consists in calculating histamine liberated by blood cells in touch with an allergen. To this day, this method is only used in Hymenoptera venom allergy diagnosis. The principle of this study is to measure histamine released by activated basophils in surnageons of Basophil Activation Test (BAT) for different allergens: Hymenoptera venoms: Bee, White Faced Hornet, Vespula Wasp. Drugs: Cefaperos, Clamoxyl, Alfatil, Rapifen, Diprivan, Nesdonal, Mivacron. A threshold of positivity (amplification factor in comparison with the control) is determined for these two classes of allergens: 45 for Hymenoptera venoms and 9 for drugs. These results, compared to the other diagnosis technics (Histamine Release, Basophil Activation Test, Prick Tests) discloses very high correlation rates in each case. This method seems to be a reliable method for Hymenoptera venom allergy diagnosis and for drugs allergy diagnosis too. However, this study is based on a few number of patients, so a significant statistic conclusion can't be expressed but it opens an interesting way of research.

  15. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Imilia Ismail

    2014-01-01

    Full Text Available Acute promyelocytic leukaemia (APL is an M3 subtype of acute myeloid leukaemia (AML. This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL.

  16. Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

    Science.gov (United States)

    Birch, J M; Swindell, R; Marsden, H B; Morris Jones, P H

    1981-03-01

    The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children's Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

  17. Research on potential radiation risks in areas with nuclear power plants in Japan: leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected municipalities

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimoto, Yasuhiko [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Yoshinaga, Shinji [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Yamamoto, Kazuhide [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Fijimoto, Kenzo [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Nishizawa, Kanae [Research Centre for Charged Particle Therapy, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Sasaki, Yasuhito [Board of Executive Directors, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan)

    2004-12-01

    The results of a geographical correlation study using Poisson regression analysis are reported for leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected Japanese municipalities with or without a nuclear power plant (NPP). The data did not support social concerns of an increased risk of malignant lymphoma in the vicinity of Japanese NPPs. However, some estimates of overall excess relative risk (ERR; relative risk minus one) were statistically significantly positive for leukaemia mortality in 20 NPP municipalities compared with mortality in the remaining 80 control areas, taking into account a minimum two-year latency following the start of commercial operation. One estimate was 0.228 (95% CI: 0.074-0.404) from a simple area adjustment using the mortality in all Japan as the external baseline rate. This superficial increase is not due to leukaemia among young people, aged less than 25 years at death. The ERR estimate for ages at death of 50-74 years was confounded to be positive for leukaemia and distorted to be negative for malignant lymphoma. For leukaemia, a positive ERR estimate was seen, especially for females and during specific periods. Confounding of the ERR estimate for two causes was also seen in some NPP areas including a high adult T-cell leukaemia (ATL) area. Temporal area variations associated with ATL misclassification and a temporal increasing trend of leukaemia mortality in the elderly caused the confounding effects. Our findings do not support the hypothesis of a leukaemogenic impact of NPPs in Japan.

  18. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

    Science.gov (United States)

    Ley, Timothy J; Mardis, Elaine R; Ding, Li; Fulton, Bob; McLellan, Michael D; Chen, Ken; Dooling, David; Dunford-Shore, Brian H; McGrath, Sean; Hickenbotham, Matthew; Cook, Lisa; Abbott, Rachel; Larson, David E; Koboldt, Dan C; Pohl, Craig; Smith, Scott; Hawkins, Amy; Abbott, Scott; Locke, Devin; Hillier, Ladeana W; Miner, Tracie; Fulton, Lucinda; Magrini, Vincent; Wylie, Todd; Glasscock, Jarret; Conyers, Joshua; Sander, Nathan; Shi, Xiaoqi; Osborne, John R; Minx, Patrick; Gordon, David; Chinwalla, Asif; Zhao, Yu; Ries, Rhonda E; Payton, Jacqueline E; Westervelt, Peter; Tomasson, Michael H; Watson, Mark; Baty, Jack; Ivanovich, Jennifer; Heath, Sharon; Shannon, William D; Nagarajan, Rakesh; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; DiPersio, John F; Wilson, Richard K

    2008-11-06

    Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

  19. Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

    Science.gov (United States)

    Laurier, D; Grosche, B; Auvinen, A; Clavel, J; Cobaleda, C; Dehos, A; Hornhardt, S; Jacob, S; Kaatsch, P; Kosti, O; Kuehni, C; Lightfoot, T; Spycher, B; Van Nieuwenhuyse, A; Wakeford, R; Ziegelberger, G

    2014-09-01

    Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

  20. Increased level of basophil CD203c expression predicts severe chronic urticaria.

    Science.gov (United States)

    Ye, Young-Min; Yang, Eun-Mi; Yoo, Hye-Soo; Shin, Yoo-Seob; Kim, Seung-Hyun; Park, Hae-Sim

    2014-01-01

    Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P basophil CD203c expression in severe CU patients was significantly higher than in non-severe CU (66.5% ± 23.3% vs 54.0% ± 23.3%, P = 0.033). Multiple logistic regression analysis indicated that both ≥ 72% basophil CD203c expression and urticaria activity score (UAS)≥ 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.

  1. Unusual cause of sudden cardiac death : Basophilic degeneration of coronary arteries

    NARCIS (Netherlands)

    Jessurun, GAJ; Tio, RA; Ribbert, LSM; Willemse, F; Boonstra, PW; Crijns, HJGM

    1996-01-01

    Basophilic or mucoid degeneration of the intima in the coronary arteries is an extremely rare cause of premature atherosclerosis. An unusual case of fatal basophilic degeneration of the coronary arteries 142 days after delivery is reported. (C) 1996 Wiley-Liss, Inc.

  2. Basophil activation test with food additives in chronic urticaria patients.

    Science.gov (United States)

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  3. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool......The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  4. In vitro histamine release from basophils of asthmatic and atopic individuals in D/sub 2/O

    Energy Technology Data Exchange (ETDEWEB)

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

    It was found that spontaneous histamine release from human basophils in H/sub 2/O-based buffers is negligible; in D/sub 2/O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D/sub 2/O release was not cytotoxic is suggested by the finding that 37/sup 0/ was optimal, with inhibition at 4/sup 0/C or 46/sup 0/C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A/sub 2/. The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D/sub 2/O release. No increase in D/sub 2/O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D/sub 2/O release was the loss of reactivity by preincubating cells at 37/sup 0/C for 30 min before adding D/sub 2/O. Non-D/sub 2/O-reactive cells could be ''converted'' to D/sub 2/O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37/sup 0/C and an inhibitor profile similar to D/sub 2/O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D/sub 2/O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear.

  5. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

  6. The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

    OpenAIRE

    2008-01-01

    Older adults with Acute Myeloid Leukaemia (AML), when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older A...

  7. Prolonged remission maintenance in acute myeloid leukaemia.

    Science.gov (United States)

    Spiers, A S; Goldman, J M; Catovsky, D; Costello, C; Galton, D A; Pitcher, C S

    1977-08-27

    Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

  8. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  9. Severe vulgaris psoriatic patients with acute myelogenous leukaemia and resolution after allogeneic bone marrow transplantation/peripheral blood stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HE Yan-ling; LU Xi-jin; QIU Jin-yin; ZHU Tie-jun

    2005-01-01

    @@ Psoriasis is a common disease with a prevalence of up to 2% in the world population.1 The pathophysiological mechanism of this inflammatory disease has not been determined although it is generally accepted to have a genetic predisposition and be T-cell mediated. The lymphocytes are the target of psoriatic therapeutic strategies. Therapy resolves psoriasis for a time, but induces some severe side effects. Some cases of severe psoriasis, treated with multiple therapeutic regimens for many years, developed leukemia.

  10. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives

    Directory of Open Access Journals (Sweden)

    Debard Anne-Lise

    2005-06-01

    Full Text Available Abstract The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient sensitivity and specificity. During recent years an increasing number of studies have demonstrated that flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting surface expression of degranulation/activation markers (CD63 or CD203c. This article reviews the recent improvements to the basophil activation test made possible by flow cytometry, focusing on the use of anti-CRTH2/DP2 antibodies for basophil recognition. On the basis of a new triple staining protocol, the basophil activation test has become a standardized tool for in vitro diagnosis of immediate allergy. It is also suitable for pharmacological studies on non-purified human basophils. Multicenter studies are now required for its clinical assessment in large patient populations and to define the cut-off values for clinical decision-making.

  11. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives.

    Science.gov (United States)

    Boumiza, Radhia; Debard, Anne-Lise; Monneret, Guillaume

    2005-06-30

    The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard) and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient sensitivity and specificity. During recent years an increasing number of studies have demonstrated that flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting surface expression of degranulation/activation markers (CD63 or CD203c). This article reviews the recent improvements to the basophil activation test made possible by flow cytometry, focusing on the use of anti-CRTH2/DP2 antibodies for basophil recognition. On the basis of a new triple staining protocol, the basophil activation test has become a standardized tool for in vitro diagnosis of immediate allergy. It is also suitable for pharmacological studies on non-purified human basophils. Multicenter studies are now required for its clinical assessment in large patient populations and to define the cut-off values for clinical decision-making.

  12. The effect of stimuli on basophil-mediated atopic responses during asthmatic lying-in women and in newborns.

    Science.gov (United States)

    Yang, Ling; Guo, Yin-Shi; Jiang, Jin-Qi; Guo, Xue-Jun; Xu, Yi-Ping; Tian, Ye; Xiong, Ying; Han, Li

    2012-08-01

    Morbidity from allergic diseases is increasing. Basophils play a critical role in systemic anaphylaxis and chronic allergic inflammation. The prenatal environment must be regarded as a possible early risk factor for allergic diseases in children. Our objective was to determine if basophils harvested from neonates genetically predisposed to atopic disease had different levels of CD63 expression and IL-4 release properties in response to various stimuli (peptidoglycan, Dermatophagoides farinae, hyperosmotic mannitol). Blood samples were collected from 16 asthmatic and 18 healthy women and their newborns. Peripheral blood basophil histamine was measured using the human basophil degranulation test (HBDT), whereas activation was assessed by flow cytometric measurement of CD63 expression on the cord blood basophil surface. IL-4 levels were quantified by ELISA following allergen stimulation. The basophil degranulation index (DI) in granulocytes harvested from the peripheral blood of asthmatic women was assessed following stimulation with peptidoglycan (PGN), Dermatophagoides farinae (Df ) extract, or hyperosmotic mannitol. The DI was significantly higher in atopic women than in healthy controls. Upregulation of CD63 on the cord blood basophil surface was also detected in response to these stimuli. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared to basophils purified from the controls. These data suggested that various stimuli play a role in augmenting allergic reactions via modulation of activated basophil cytokine secretion. It may require new methods to stabilize the basophils in allergic diseases.

  13. In vitro evaluation of the anti-proliferative activities of the wood essential oils of three Cedrus species against K562 human chronic myelogenous leukaemia cells.

    Science.gov (United States)

    Saab, Antoine M; Lampronti, Ilaria; Borgatti, Monica; Finotti, Alessia; Harb, Faouzi; Safi, Samir; Gambari, Roberto

    2012-01-01

    There are four kinds of Cedar: Cedrus libani naturally occurring in Lebanon, Syria and Turkey, Cedrus atlantica in Morocco and Algeria, Cedrus brevefolia in Cyprus Island and Cedrus deodara which is distributed in Himalayan Mountains. Wood essential oils obtained from C. libani, C. atlantica and C. deodara were tested for the inhibition of K562 cell proliferation and for the induction of erythroid differentiation. The wood essential oils of C. libani, C. atlantica and C. deodara inhibited the proliferation of the K562 cell line exhibiting IC(50) values 23.38 ± 1.7, 59.37 ± 2.6 and 37.09 ± 1.4 µg mL(-1), respectively. Meanwhile, C. libani wood oils induced a percentage of erythroid differentiation of 15 ± 2% at concentration 5 µg mL(-1). Cedrus deodara wood oil indicated a percentage of erythroid differentiation of 20 ± 2% at concentration 25 µg mL(-1) and C. atlantica wood oils showed a percentage of erythroid differentiation of 12 ± 1.8% at concentration 10 µg mL(-1).

  14. Increased Level of Basophil CD203c Expression Predicts Severe Chronic Urticaria

    OpenAIRE

    Ye, Young-Min; Yang, Eun-Mi; Yoo, Hye-Soo; Shin, Yoo-Seob; Kim, Seung-Hyun; Park, Hae-Sim

    2013-01-01

    Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal con...

  15. Acute leukaemia following malignant ependymoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pai, M.R.; Advani, S.H.; Gopal, R.; Nair, C.N.; Saikia, T.; Kamat, D.M.

    1985-05-01

    Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here the authors report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.

  16. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia.

    Science.gov (United States)

    Park, Jung Eun; Yuen, Hiu Fung; Zhou, Jian Biao; Al-Aidaroos, Abdul Qader O; Guo, Ke; Valk, Peter J; Zhang, Shu Dong; Chng, Wee Joo; Hong, Cheng William; Mills, Ken; Zeng, Qi

    2013-09-01

    FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.

  17. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

    Directory of Open Access Journals (Sweden)

    V Adam Cruickshank

    Full Text Available Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

  18. The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Attilio Olivieri

    2008-06-01

    Full Text Available Older adults with Acute Myeloid Leukaemia (AML, when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients.Pacientes idosos com leucemia mielóide aguda (LMA, quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao

  19. The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

    Science.gov (United States)

    Steiner, Markus; Huber, Sara; Harrer, Andrea

    2016-01-01

    Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology. PMID:28078302

  20. Increasing time interval and decreasing allergen dose interval improves ex vivo desensitization of human blood basophils

    DEFF Research Database (Denmark)

    Witting Christensen, Sara K; Krohn, Inge Kortekaas; Thuraiaiyah, Jani;

    2016-01-01

    BACKGROUND: Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established. METHODS: Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing...... allergen concentrations. At each step basophil activation (CD193(+) CD63(+) ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to a single-dose desensitization protocols with threshold and subthreshold...... allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol. RESULTS: Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocols did not reduce basophil activation...

  1. Surface profiling of normally responding and nonreleasing basophils by flow cytometry

    DEFF Research Database (Denmark)

    Kistrup, Kasper; Poulsen, Lars Kærgaard; Jensen, Bettina Margrethe

    Background Human basophils are granulocytes with the capacity to play important roles in allergy for example by releasing histamine when activated by cross-linking of their high affinity IgE receptors (Fc¿RI). However, not all individuals have basophils responding with a histamine release after......c, C3aR, C5aR CCR3, FPR1, ST2, CRTH2 on anti-IgE respondsive and nonreleasing basophils by flow cytometry, thereby generating a surface profile of the two phenotypes. Methods Fresh buffy coat blood (histamine release and nonreleases were defined as having...... a maximum release basophils, defined as FceRIa+CD3-CD14-CD19-CD56-,were analysed for surface expression of relevant markers. All samples were compensated and analysed in logicle display. All gates...

  2. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  3. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Trněný Marek

    2011-10-01

    Full Text Available Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in

  4. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives

    OpenAIRE

    Debard Anne-Lise; Boumiza Radhia; Monneret Guillaume

    2005-01-01

    Abstract The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard) and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient...

  5. Acute myelomonocytic leukaemia with short-term spontaneous remission in a cat.

    Science.gov (United States)

    Mylonakis, M E; Petanides, T A; Valli, V E; Vernau, W; Koytinas, A F; Michael, R S

    2008-06-01

    A 2-year-old, spayed female domestic shorthair cat was referred with a history of anorexia and depression of 1 week duration. On physical examination, the cat was lethargic and febrile, with splenomegaly, anisocoria and ulcerative stomatitis. A complete blood count (CBC) and a biochemistry profile showed leukocytosis, numerous blast cells in the peripheral blood, thrombocytopenia, hyperglobulinaemia and a positive test for feline leukaemia virus antigen. A diagnosis of acute myelomonocytic leukaemia was made on the basis of the results of bone marrow cytology, histopathology, and immunochemistry (CD3, CD79a, lysozyme, and myeloperoxidase) tests. Following an unexpected 1-month period of clinical and clinicopathological remission without chemotherapy, the cat relapsed and died 1 week later.

  6. Effects of Echium plantagineum L. Bee Pollen on Basophil Degranulation: Relationship with Metabolic Profile

    Directory of Open Access Journals (Sweden)

    Eduarda Moita

    2014-07-01

    Full Text Available This study aimed to evaluate the anti-allergic potential of Echium plantagineum L. bee pollen and to characterize its primary metabolites. The activity of E. plantagineum hydromethanolic extract, devoid of alkaloids, was tested against β-hexosaminidase release in rat basophilic leukemic cells (RBL-2H3. Two different stimuli were used: calcium ionophore A23187 and IgE/antigen. Lipoxygenase inhibitory activity was evaluated in a cell-free system using soybean lipoxygenase. Additionally, the extract was analysed by HPLC-UV for organic acids and by GC-IT/MS for fatty acids. In RBL-2H3 cells stimulated either with calcium ionophore or IgE/antigen, the hydromethanolic extract significantly decreased β-hexosaminidase release until the concentration of 2.08 mg/mL, without compromising cellular viability. No effect was found on lipoxygenase. Concerning extract composition, eight organic acids and five fatty acids were determined for the first time. Malonic acid (80% and α-linolenic acid (27% were the main compounds in each class. Overall, this study shows promising results, substantiating for the first time the utility of intake of E. plantagineum bee pollen to prevent allergy and ameliorate allergy symptoms, although a potentiation of an allergic response can occur, depending on the dose used.

  7. IgE-mediated 15-hydroxyeicosatetraenoic acid (15-HETE) generation by peripheral blood leukocytes: its association with basophil activation

    OpenAIRE

    Michalak, Anna; Lewandowska-Polak, Anna; Moskwa, Sylwia; Kowalski, Marek L; Grzegorczyk, Janina Ł.

    2015-01-01

    Introduction Allergen-induced basophil activation has been associated with the release of several mediators and with an increased expression of CD203c molecules on basophils. Aim To assess the influence of specific allergens on the generation of 15-hydroxyeicosatetraenoic (15-HETE) from peripheral blood leukocytes in relation to basophil activation, on the basis of CD203c molecule expression and histamine release. Material and methods The study included 15 patients with clinical symptoms of b...

  8. Basophil count, a marker for disease activity in systemic lupus erythematosus.

    Science.gov (United States)

    Liang, Peifen; Tang, Ying; Fu, Sha; Lv, Jun; Liu, Bo; Feng, Min; Li, Jinggao; Lai, Deyuan; Wan, Xia; Xu, Anping

    2015-05-01

    Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease, with frequent flares amid remissions. Basophils contribute to the immunopathogenesis of SLE. This retrospective clinical study evaluated blood basophil count as a potential marker of SLE activity. This study included 213 patients with SLE, 70 with non-SLE chronic kidney disease (CKD), and 100 healthy volunteers. SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Baseline and post-immunosuppressant bioparameters were compared in patients with active SLE, with second samples taken at total SLEDAI ≤4. Blood basophil counts and other conventional biomarkers were compared among the groups. Among the 213 SLE patients (192 women, 21 men; mean age 33.0 ± 12.0 years), 149 had active disease. Basophil counts were significantly lower in patients with SLE than in patients with non-SLE CKD and healthy controls (0.009 ± 0.010 vs. 0.025 ± 0.015 vs. 0.022 ± 0.010 × 10(9)/L, p Basophil counts in SLE patients were significantly higher after than before immunosuppressive treatment (0.021 ± 0.017 vs. 0.008 ± 0.008 × 10(9)/L, p analysis showed that basophil counts were similar to conventional markers (leukocytes, platelets, and double-stranded (ds) DNA IgG) in differentiating active from inactive SLE. These findings indicate that blood basophil counts may be a useful biomarker in evaluating SLE activity.

  9. Abscopal induction of leukaemia and osteosarcoma following administration of alpha-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Lord, B.I. (Paterson Institute for Cancer Research, Christie Hospital Manchester, Manchester (United Kingdom))

    2008-12-15

    Alpha-particle-emitting, bone-seeking radionuclides can induce leukaemia and/ or osteosarcoma in mice. Furthermore, plutonium-239, given to male mice before mating with normal females, while not directly leading to leukaemia in the progeny does lead to enhanced susceptibility to leukaemogenic agents. In the first case, the amounts of radionuclide are very small in experimental terms; and zero in the case of transgenerational activity. In both cases, the development of the disorders is remote in time and location relative to that of the contaminating radionuclide, making interpretation of the mechanisms and estimation of radiation risk problematic. It is necessary, then, to address questions involving the basis of haemopoiesis itself. Cellular kinetics of the development of blood from the pluripotent stem cells to the mature functional cells are outlined, describing compensatory proliferation mechanisms and extensive movement of cells throughout the marrow space. The locations of potential oncogenic target cells are identified and the nature of the stromal microenvironment that regulates haemopoiesis is defined. Plutonium-239, given to male mice, targets spermatogenesis at the stem cell level leaving unidentified damage that is inherited by his offspring. This leaves the offspring susceptible to a leukaemogenic agent encountered later in life. The characteristics of this, corroborated by consideration of the cellular kinetics, are of an inherited genomic instability. Cells of the microenvronment, inheriting the same genetic damage, probably act in the role of an enhancing 'bystander'. In adult mice, the mechanisms are different. Bone turnover results in radioactivity being gradually transported through the marrow by long-lived macrophages. A model based on temporal microdistributions of activity, defining specific target cell regions, is able to illustrate that considering bone marrow as a uniform mass of cells is inadequate to describe the observed

  10. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    OpenAIRE

    Nahid Eskandari; Reza Bastan; Maryam Ahmadi; Peachell, Peter T

    2014-01-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enric...

  11. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    Science.gov (United States)

    Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.

  12. [Biphenotypic acute leukaemia with Burkitt-like cytology].

    Science.gov (United States)

    Coche, D; Bergues, B; Harrivel, V; Guillaume, N

    2009-01-01

    Biphenotypic acute leukaemia (BAL) represents about 5% of adult acute leukaemia. Based on a previously described scoring system, the European Group for Immunologic Classification of Leukaemia (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based on the number and degree of the specificity of several markers for myeloid or T/B lymphoid blasts. Here, we report the case of a BAL with Burkitt-like cytology, corresponding to "the acute lymphoblastic leukaemia, Burkitt type" L3 for the FAB classification. By flow cytometry, the blasts showed a positivity for B lymphoid cytoplasmic (CD79a and mu) and membrane (CD19, CD22, CD24, IgM) markers AND a positivity for the myeloid (CD13, CD33, CD65, CD15) markers.

  13. Trace elements in scalp hair of leukaemia patients

    Directory of Open Access Journals (Sweden)

    Khuder Ali

    2014-08-01

    Full Text Available The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in all studied leukaemia patients. The median rank obtained by Mann-Whitney U-test revealed insignifi cant differences between the leukaemia patients subgroups and the controls. An exact probability (α 0.70 in the scalp hair of control group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn, Pb/Fe-Pb, Cu/Ni-Zn/Ni, Cu/Ni-Pb/Ni, Zn/Ni-Pb/Ni, Zn/Fe-Zn/Cu, Pb/Ni-Ni and Ni/Fe-Pb/Ni, whereas only very strong positive ratios in the scalp hair of leukaemia patients group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn and Pb/Fe-Pb, all correlations were signifi cant at p < 0.05. Other strong and signifi cant correlations were also observed in scalp hair of both groups. Signifi cant differences between grouping of studied TEs in all classifi ed leukaemia groups and controls were found using principal component analysis (PCA. The results of PCA confi rmed that the type and the growth of leukaemia factors were more important in element loading than the age factor.

  14. Adrenal crisis in a patient with acute myeloid leukaemia

    OpenAIRE

    Li, Wang; Okwuwa, Ikemefuna; Toledo-Frazzini, Karla; Alhomosh, Alaaedin

    2013-01-01

    Adrenal crisis is a group of clinical manifestation predominantly with hypotensive shock, electrolyte imbalance in a patient with adrenal insufficiency or in a patient who was abruptly withdrawn from glucocorticoid treatment acute myeloid leukaemia (AML) is one of the most common acute leukaemia in adults. Though the above diseases are commonly seen in individual patients, the coexistence of both conditions in the same patient is rare. We reported a 64-year-old African-American man with a his...

  15. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    OpenAIRE

    Cartwright, R. A.; Bernard, S.M.; Bird, C. C.; Darwin, C. M.; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-01-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, im...

  16. Serum Specific IgE to Thyroid Peroxidase Activates Basophils in Aspirin Intolerant Urticaria.

    Science.gov (United States)

    Shin, Yoo Seob; Suh, Dong-Hyeon; Yang, Eun-Mi; Ye, Young-Min; Park, Hae-Sim

    2015-06-01

    Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.

  17. Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy.

    Science.gov (United States)

    González-Muñoz, Miguel; Villota, Julian; Moneo, Ignacio

    2008-06-01

    Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non-allergic children (n = 9). Allergen-induced basophil activation was detected as a CD63-upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value of activated basophils discriminating mite allergic and non-allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite-sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97-1.01, p Analysis of the data obtained with 1.6 microg/ml mite extract defined a cut-off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91-1.01; p basophils (AUC = 1.0) with 16 microg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 microg/ml extract (AUC = 97%, 95% CI = 0.92-1.02; p basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1-specific IgE (>100 kU/l). Cross-reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA-CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen-induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity

  18. Impact of thermal processing and the Maillard reaction on the basophil activation of hazelnut allergic patients.

    Science.gov (United States)

    Cucu, Tatiana; De Meulenaer, Bruno; Bridts, Chris; Devreese, Bart; Ebo, Didier

    2012-05-01

    Food allergy, an abnormal immunological response due to sensitization to a food component, has become an important health problem, especially in industrialized countries. The aim of this study was to investigate the impact of thermal processing and glycation on the basophil activation by hazelnut proteins using a basophil activation test. Patients with systemic allergic reactions (SR; n=6) to hazelnut as well as patients with an isolated oral allergy syndrome (OAS; n=4) were investigated. Thermal processing of hazelnut proteins either in the presence or absence of wheat proteins did not result in major changes in the stimulatory activity of the basophils for patients with SR or OAS. For the patients with OAS, incubation of hazelnut proteins with glucose led to complete depletion of the stimulatory activity of the basophils. An increase in stimulatory activity of the basophils for two out of six patients with SR was observed. For the other four patients slight or complete abolition of the stimulatory activity was observed. These results indicate that some patients with SR to hazelnut are at risk when exposed to hazelnut proteins, even in processed foods.

  19. L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection

    Science.gov (United States)

    The aim of this paper was to investigate the role of porcine basophils in protective immunity. Experimental pigs were infected with 1,000 Ascaris suum eggs daily for 21 days. Control pigs were maintained helminth-free. Circulating porcine basophils were isolated from the anti-coagulated whole blood ...

  20. Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility

    OpenAIRE

    Salete Smaniotto; Elke Schneider; Nicolas Goudin; Rachel Bricard-Rignault; François Machavoine; Mireille Dardenne; Michel Dy; Wilson Savino

    2013-01-01

    Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (...

  1. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  2. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  3. Boronated monoclonal antibodies for potential neutron capture therapy of malignant melanoma and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tamat, S.R.; Patwardhan, A.; Moore, D.E.; Kabral, A.; Bradstock, K.; Hersey, P.; Allen, B.J.

    The authors report a preparation and characterisation of boronated melanoma and leukaemia antibodies and the separation from native antibody by anion exchange liquid chromatography. Two types of biodistribution experiments were performed with the boronated melanoma antibody 225.28S using Balb/c derived nude mice in which melanoma tumours had been raised in the thigh by subcutaneous injection of a human malignant melanoma cell line, designated CMC. From these experiments, one may conclude that the boronated antibody has the ability to localise in the melanoma following systemic injection, but more efficient use of the preparation is achieved with perilesional administration.

  4. Autologous serum skin test reactivity and basophil histamine release test in patients with nasal polyposis: preliminary results.

    Science.gov (United States)

    Zambetti, G; Ciofalo, A; Soldo, P; Fusconi, M; Romeo, R; Greco, A; Altissimi, G; Macri, G F; Marinelli, C; Pagliuca, G; De Vincentiis, M

    2010-01-01

    An eosinophilic inflammatory process is generally observed in patients suffering from nasal polyposis (NP), however its onset has not yet been defined. It has been suggested that immune activation of inflammatory cells may be the cause. The aim of this study is to verify whether autoantibodies and/or histamine-releasing factors are present in the serum of patients suffering from NP. In fact, we assume that autoantibodies and/or histamine-releasing factors, as already demonstrated in chronic idiopathic urticaria and asthma, may be involved in the pathogenesis of NP. In this case-control analytical study 40 patients with NP and 27 control subjects underwent the in vivo autologous serum skin test (ASST). The sera from 6 patients suffering from NP and 9 control group subjects, who had all been previously studied and randomly selected, underwent basophil histamine release assay from normal donor as a pilot study. The ASST showed positive results in 55% of patients suffering from NP versus 8% of the control group (p= .00006), the basophil histamine release test (BHRT) turned out positive in all patients tested and in 11% of the control group. We found a weak positive correlation between the percentage of histamine release and the wheal diameter. ASST reactivity is very frequent in patients suffering from NP, thus suggesting the presence of histamine-releasing factors in the blood stream. The BHRT was positive in the serum of all patients, thus suggesting the presence of anti-FcepsilonRI, anti-IgE autoantibodies and/or other histamine-releasing factors, the presence of which can play a role in triggering and maintaining the eosinophilic inflammatory process in NP.

  5. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  6. Biochemical and functional characterization of proteoglycans isolated from basophils of patients with chronic myelogenous leukemia.

    Science.gov (United States)

    Metcalfe, D D; Bland, C E; Wasserman, S I

    1984-04-01

    Human basophils were obtained from three donors with myelogenous leukemia. Proteoglycans were labeled by using [35S]sulfate as precursor and were extracted in 1 M NaCl with protease inhibitors to preserve their native structure. [35S]proteoglycans filtered on Sepharose 4B with an average m.w. similar to that of a rat heparin proteoglycan that has an estimated m.w. of 750,000. The [35S]glycosaminoglycan side chains filtered with an average m.w. slightly smaller than a 60,000-m.w. glycosaminoglycan marker. The [35S]glycosaminoglycans were resistant to heparinase and susceptible to degradation by chondroitin AC lyase and chondroitin ABC lyase. The intact [35S]glycosaminoglycans chromatographed on DEAE Sepharose as a single peak eluting just before an internal heparin marker. These findings indicate that the [35S]glycosaminoglycans were made up only of chondroitin sulfates. No heparin was identified. The chondroitin sulfate disaccharides that resulted from the action of chondroitin ABC lyase on the basophil glycosaminoglycans consisted of 92% delta Di-4S, 6% delta Di-6S, and 2% disulfated disaccharides. The [35S]chondroitin sulfate proteoglycans were susceptible to cleavage with proteases and could be shown to be released intact from basophils during degranulation initiated by the calcium ionophore A23187. The basophil proteoglycans and glycosaminoglycans were capable of binding histamine in water, but not in phosphate-buffered saline, and had no anticoagulant activity.

  7. A Case of Anaphylactic Reaction Following Matsutake Mushroom Ingestion: Demonstration of Histamine Release Reaction of Basophils

    Directory of Open Access Journals (Sweden)

    Takako Toda

    2010-01-01

    Discussion: Matsutake mushroom can, on rare occasions, cause anaphylaxis in sensitized people, a reaction so far observed only in Japan. Not ony the in vivo prick-to-prick test but also the in vitro basophil activation test utilizing the patient's blood represent useful methods for allergen identification and also for identification of sensitized subjects.

  8. Allergy to formaldehyde: basophil histamine-release test is useful for diagnosis.

    Science.gov (United States)

    Tanaka, Yusuke; Nakase, Yuko; Yamaguchi, Masao; Sugimoto, Naoya; Ohara, Kenshin; Nagase, Hiroyuki; Ohta, Ken

    2014-01-01

    We describe a case of formaldehyde-induced urticaria with a positive test result for serum IgE antibody against this substance. Formaldehyde's slow protein-binding property may explain why basophil histamine-release tests using fresh formaldehyde solutions are not diagnostic, whereas the tests are useful if formaldehyde that had been stored with albumin is used.

  9. Distribution and dynamics of rat basophilic leukemia immunoglobulin E receptors (FcepsilonRI) on planar ligand-presenting surfaces.

    Science.gov (United States)

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A; Wilson, Bridget S; Timlin, Jerilyn A; Thomas, James L

    2010-07-21

    There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcepsilonRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (+/-50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D approximately 10(-1) microm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes.

  10. Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression

    Directory of Open Access Journals (Sweden)

    Wiebe Thomas

    2008-08-01

    Full Text Available Abstract Background Childhood pre-B acute lymphoblastic leukemia (ALL is a bone marrow (BM derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB. Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.

  11. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

    Directory of Open Access Journals (Sweden)

    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  12. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Bernard, S M; Bird, C C; Darwin, C M; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-07-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

  13. Human retroviruses in leukaemia and AIDS: reflections on their discovery, biology and epidemiology.

    Science.gov (United States)

    Karpas, Abraham

    2004-11-01

    The study of retroviruses has had a profound impact by unveiling an unusual form of viral replication: the multiplication of RNA viruses via a proviral DNA, for which Jan Svoboda provided the experimental model over forty years ago. In 1970 Temin, Mizutani and Baltimore discovered that this group of viruses contains a unique enzyme catalysing the synthesis of a DNA copy of the viral RNA: reverse transcriptase (RT). The discovery of RT has itself had an enormous impact on molecular biology in general, but also stimulated many premature claims of its detection in human disease. Claims by Gallo's laboratory that the cytoplasm of human leukaemia cells contained RT proved to be unfounded, as did his report in collaboration with Weiss that myeloid leukaemia contained HL23 virus, this organism proving not to be human but a laboratory contaminant of three monkey viruses. Conclusive demonstration of a retroviral involvement in human leukaemia was first provided in 1981 by Hinuma and his associates, showing that adult T-cell leukaemia (ATL), a rare form of leukaemia endemic to south-west Japan, is caused by a new retrovirus (ATLV). Other publications in December 1980 and through 1981 claimed the discovery of a new human T-cell leukaemia virus involved in mycosis fungoides (MF) and Sézary's syndrome (SS). This virus was termed HTLV by Gallo. The nucleotide sequence of ATLV is strongly conserved, that of my 1983 isolate from a black British ATL patient being practically identical with the Japanese virus isolates. After AIDS was recognised in 1981 by Gottlieb and coworkers as a new human disease, several papers were published by Gallo and his associates during 1983-4, invoking the oncovirus responsible for adult T-cell leukaemia as the cause of AIDS. In 1983 the French scientist Barré-Sinoussi and her colleagues succeeded in isolating a new agent in the disease, a lentivirus, which they named LAV. The French immunologist Klatzmann and his colleagues discovered that LAV killed

  14. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

    Science.gov (United States)

    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

  15. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  16. The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures

    Directory of Open Access Journals (Sweden)

    Friederike Hörnig

    2016-01-01

    Full Text Available Purpose. Enhanced eosinophil/basophil (Eo/B progenitor cell levels are known to be associated with allergic inflammation and atopy risk. The aim of the present study was to investigate the influence of different indoor exposures on the recruitment and differentiation of Eo/B progenitors in mother-child pairs. Methods. In 68 mother-child pairs of the LINA study peripheral blood mononuclear cells were used to assess Eo/B colony forming units (CFUs. Information about disease outcomes and indoor exposures was obtained from questionnaires. Indoor concentrations of volatile organic compounds (VOCs were measured by passive sampling. Results. Infant’s Eo/B CFUs were positively associated with exposure to tobacco smoke, disinfectants, or VOCs. In contrast, for maternal Eo/B CFUs, only a few associations were seen. Higher numbers of infant Eo/B CFUs were observed in children with wheezing symptoms within the second year of life. Conclusions. We demonstrate that infant’s hematopoietic cells seem to respond with more sensitivity to environmental exposure compared to maternal cells. At least in infants, an activation of these hematopoietic cells by environmental exposure could contribute to an enhanced risk for the development of respiratory outcomes.

  17. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  18. The Effect of Stimuli on Basophil-Mediated Atopic Responses During Asthmatic Lying-In Women and in Newborns

    OpenAIRE

    Yang, Ling; Guo, Yin-Shi; Jiang, Jin-Qi; Guo, Xue-jun; Yi-ping XU; Tian, Ye; Xiong, Ying; Han, Li

    2012-01-01

    Morbidity from allergic diseases is increasing. Basophils play a critical role in systemic anaphylaxis and chronic allergic inflammation. The prenatal environment must be regarded as a possible early risk factor for allergic diseases in children. Our objective was to determine if basophils harvested from neonates genetically predisposed to atopic disease had different levels of CD63 expression and IL-4 release properties in response to various stimuli (peptidoglycan, Dermatophagoides farinae,...

  19. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species....

  20. Chronic myeloid leukemia presenting with absence of basophils and marked dyspoiesis

    Directory of Open Access Journals (Sweden)

    Anand M

    2003-01-01

    Full Text Available A 61-year old woman presented to us with fever, weakness and ecchymotic patches for one year. She had leucocytosis, anemia and thrombocytopenia. Peripheral blood smear showed 62% neutrophils, 32% myelocytes and metamyelocytes, 2% promyelocytes, 1% blasts, 2% monocytes, 1% lymphocytes but no basophils and marked dyspoiesis. Bone marrow picture was essentially the same. A diagnosis of atypical chronic myeloid leukemia was suggested. The correct diagnosis of chronic myeloid leukemia - accelerated phase was, however, made on cytogenetic analysis which showed Philadelphia chromosome (Ph and isochromosome 17q [i(17q]. This case describes a rare and diagnostically difficult presentation of CML arising out of a combination of prominent dyspoiesis and near absence of peripheral blood basophils.

  1. Basophil activation test by flow cytometry: present and future applications in allergology.

    Science.gov (United States)

    Ebo, D G; Bridts, C H; Hagendorens, M M; Aerts, N E; De Clerck, L S; Stevens, W J

    2008-07-01

    The diagnosis of allergic reactions in clinical practice rests upon both clinical history and the demonstration of specific immunoglobulin E (sIgE), either in the serum or via skin tests. However, for various reasons, identification of the offending allergen(s) is not always possible. Moreover, not all allergies are IgE-mediated. In an attempt to find reliable methods to investigate hypersensitivity reactions, histamine and sulfidoleukotriene release tests have long been introduced. However, relatively few comprehensive quality reports have been published so far. Upon challenge with a specific allergen, basophils not only secrete quantifiable bioactive mediators but also upregulate the expression of different markers which can be detected efficiently by flow cytometry using specific monoclonal antibodies. This review addresses the principals, particular technical aspects and pitfalls as well as the clinical and research applications of flow-assisted analysis of in vitro activated basophils.

  2. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

    2011-07-15

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  3. Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects of inflammatory cells

    NARCIS (Netherlands)

    Beek, van L.M.; Mulder, M.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparation

  4. Basophil activation test in the study of food and drug hypersensitivity reactions

    OpenAIRE

    Carrapatoso, I; Cadinha, S; Sanz, ML

    2005-01-01

    The increase in the prevalence of adverse reactions to foods and drugs represents a constant challenge to the development of new methods of diagnosis. A meta-analysis on published studies concerning the clinical usefulness of the Basophil activation test (BAT) in these reactions was performed. High sensibilities and specificities can be achieved if certain technical requirements are observed. BAT results have a positive and high significant correlations with other routine diagnostic ...

  5. A Case of Anaphylactic Reaction Following Matsutake Mushroom Ingestion: Demonstration of Histamine Release Reaction of Basophils

    OpenAIRE

    Takako Toda; Masao Yamaguchi; Yuko Nakase; Naoya Sugimoto; Maho Suzukawa; Hiroyuki Nagase; Ken Ohta

    2010-01-01

    Background: Matsutake mushroom is not recognized as a common food allergen. However, several case reports have suggested that this mushroom can induce anaphylaxis on rare occasions. Case Summary: We report a woman with bronchial asthma, who experienced two episodes of Matsutake-induced anaphylaxis. Both the prick-to-prick test and basophil histamine release test showed positive reactions to this mushroom in this patient, but not in control subjects. Discussion: Matsutake mushroom can, o...

  6. Study of clinical, haematological and cytogenetic profile of patients with acute erythroid leukaemia

    Science.gov (United States)

    Linu, Jacob Abraham; Udupa, MS Namratha; Madhumathi, DS; Lakshmaiah, KC; Babu, K Govind; Lokanatha, D; Babu, MC Suresh; Lokesh, KN; Rajeev, LK; Rudresha, AH

    2017-01-01

    Background Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting cytogenetic profile of this disease, considering the rarity of its occurrence and poor prognosis. Materials and methods This study was done by retrospective analysis of data from 32 case files of patients diagnosed with AEL. Clinical details noted down were the demographic profile, peripheral blood smear details and bone marrow examination details: (1) blasts-erythroblasts and myeloblasts, (2) dysplasia in the cell lineages and (3) cytogenetic abnormalities. Results The most common presenting symptom was fever. Pancytopenia at presentation was seen in 81.25% of patients. Dysplasia was observed in bone marrow in 100% of erythroblasts and in 40% of myeloblasts in erythroid/myeloid subtype. In pure myeloid subtype, myeloid and megakaryocytic dysplasias were not obvious. Complex karyotype was noticed only in patients of pEL. Conclusion AEL is a rare group of heterogeneous diseases with many neoplastic and non-neoplastic conditions mimicking the diagnosis. The clinical presentation and cytogenetics are also non-specific, presenting additional challenges to the diagnosis. PMID:28144286

  7. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  8. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Laurier, D [Institute for Radiation Protection and Nuclear Safety, IRSN/DRPH/SRBE, BP 17, 92262 Fontenay aux Roses cedex (France); Hemon, D; Clavel, J [INSERM Unit 754, Villejuif (France)], E-mail: Dominique.laurier@irsn.fr

    2008-09-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants. (note)

  9. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants.

    Science.gov (United States)

    Laurier, D; Hémon, D; Clavel, J

    2008-09-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants.

  10. 578 Comparison of the Modified Autologous Serum Skin Test and the Cd63 Basophil Activation Test in Chronic Urticaria

    OpenAIRE

    Irinyi, B; Gyimesi, E.; Garaczi, E.; Bata, Zs.; Hodosi, K.; Zeher, M; Remenyik, É.; Szegedi, A.

    2012-01-01

    Background The modified CD63 basophil activation test in the diagnosis of chronic autoimmun urticaria was first described in 2004 by Szegedi et al. We demonstrated that the strongly sensitized basophils of atopic donors can be successfully used without the addition of IL-3 for the in vitro evaluation of autoimmun urticaria. Positive correlation was found between the basophil CD63 expression test and the autolog serum skin test (ASST), and between the CD63 test and the gold standard histamine ...

  11. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian;

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant...... of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation...

  12. GOOD OUTCOME FOR VERY HIGH RISK ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA CARRYING GENETIC ABNORMALITIES t(4;11(q21;q23 or t(9;22(q34;q11, IF PROMPTLY SUBMITTED TO ALLOGENEIC TRANSPLANTATION, AFTER OBTAINING A GOOD MOLECULAR REMISSION.

    Directory of Open Access Journals (Sweden)

    Matteo Parma

    2015-05-01

    Full Text Available Background and Objectives: Acute lymphoblastic leukaemia (ALL carrying t(9;22 or t(4;11 genetic abnormalities represents a very high risk subtype of disease (VHR-ALL. Hematopoietic stem cell transplantation (HSCT still remains the only curative option also in the Imatinib era. In the last years low molecular level of minimal residual disease (MRD before HSCT was reported as one of the best favourable indexes for survival in ALL. Here we observed that even these patients can show a favourable outcome, if submitted to HSCT with very low MRD. Methods: We considered 18 consecutive VHR-ALL patients eligible to HSCT. 16 of them were transplanted upon first remission, as soon as possible, employing myelo-ablative conditioning regimens. Molecular MRD has been evaluated before and after HSCT.Results: Immediately before HSCT MRD revealed: complete molecular remission (MRDneg for 5 patients and a level <1x10-3 for 7 patients; 100 days after HSCT we had: MRDneg for 7 patients and a decrease for all the others after HSCT. After tapering of immunosuppressive drugs, 13 patients reached the MRDneg in a median time of 8 months (range 3-16; Based on intention to treat analysis: 14/18 patients are alive and disease free at the time of analysis, overall survival and event free survival is of 78% and 66% respectively, with an average follow-up of 45 months (range 6-84 since HSCT. Conclusion: Early transplantation with low MRD level seems to be correlated with a favourable outcome also in VHR-ALL

  13. A 17-gene stemness score for rapid determination of risk in acute leukaemia.

    Science.gov (United States)

    Ng, Stanley W K; Mitchell, Amanda; Kennedy, James A; Chen, Weihsu C; McLeod, Jessica; Ibrahimova, Narmin; Arruda, Andrea; Popescu, Andreea; Gupta, Vikas; Schimmer, Aaron D; Schuh, Andre C; Yee, Karen W; Bullinger, Lars; Herold, Tobias; Görlich, Dennis; Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Cheok, Meyling; Preudhomme, Claude; Dombret, Herve; Metzeler, Klaus; Buske, Christian; Löwenberg, Bob; Valk, Peter J M; Zandstra, Peter W; Minden, Mark D; Dick, John E; Wang, Jean C Y

    2016-12-15

    Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials. The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance. Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC(+) and 89 LSC(-) cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.

  14. High-flow priapism in acute lymphatic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

    2004-07-01

    Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

  15. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.

    Science.gov (United States)

    Awasthi, Aradhana; Ayello, Janet; Van de Ven, Carmella; Elmacken, Mona; Sabulski, Anthony; Barth, Matthew J; Czuczman, Myron S; Islam, Humayun; Klein, Christian; Cairo, Mitchell S

    2015-12-01

    Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, (P = 0·001), Raji4RH 19·7 ± 2·2% vs. 7·9 ± 1·5% (P = 0·001) and U-698-M 47·3 ± 4·9% vs. 23·2 ± 0·5% (P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% (P = 0·001), Raji-4RH 40·0 ± 1·6% vs. 0·5 ± 1·1% (P = 0·001) and U-698-M 70·0 ± 1·6% vs. 45·5 ± 0·1% (P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0·05), Raji4RH (P = 0·02) and U698-M (P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL.

  16. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  17. Acute lymphoblastic leukaemia after treatment of nephrotic syndrome with immunosuppressive drugs.

    Science.gov (United States)

    Kuis, W; de Kraker, J; Kuijten, R H; Donckerwolcke, R A; Voûte, P A

    1976-06-01

    The authors present a 4-year-old girl with nephrotic syndrome who developed actue lymphoblastic leukaemia 5 months after the start of a combined treatment of alternate day prednisone and daily cyclophosphamide during 3 months. The nephrotic syndrome was due to focal segmental glomerulosclerosis. The occurrence of leukaemia might be related to the preceeding treatment with cyclophosphamide.

  18. CBL mutations do not frequently occur in paediatric acute myeloid leukaemia

    NARCIS (Netherlands)

    Coenen, Eva A.; Driessen, Emma M. C.; Zwaan, C. Michel; Stary, Jan; Baruchel, Andre; de Haas, Valerie; de Bont, Eveline S. J. M.; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Arentsen-Peters, Susan T. C. J. M.; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; Stam, Ronald W.; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in pa

  19. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  20. The clinical values of peripheral blood basophil activation test in children with allergic diseases%过敏性疾病患儿外周血嗜碱性粒细胞百分比及活化率检测

    Institute of Scientific and Technical Information of China (English)

    杨皓征; 曹兰芳; 王利民

    2011-01-01

    Objective To explore the clinical values of basophil activation test in childhood allergic diseases by the analysis of CRTH2+ cells, percent of basophil, and activation of basophil in peripheral blood.Methods The peripheral basophils activation in healthy children and allergic patients ( asthma and/or rhinitis and/or dermatitis ) were analyzed with a combination of CD3/CRTH2/CD63 antibodies by flow cytometric.Results Ninty-three subjects ( 25 in control group, 68 in allergy group ) completed the study.The peripheral CRTH2+ cell level in the allergy group ( 0.53% ± 0.22% ) was significantly higher than that in control group ( 0.44% ± 0.14% )( P < 0.05 ).The peripheral basophil level of the allergy group ( 0.39% ± 0.19% ) was significantly higher than that of control group ( 0.130% ± 0.073% )( P < 0.01 ).The basophil activation ratio was higher in allergic patients ( 85.77% ± 10.63% ) than that in control group ( 31.62% ± 17.41% ).In addition, Spearman correlation coefficients indicated a moderate positive correlation between basophil activation ratio and slgE calss categorized by Unicap calss.Moreover, Spearman correlation coefficients indicated medium positive correlation between basophil activation ratio and standardized skin prick test.Conclusions The peripheral CRTH2+ cell level and basophil level increase in allergic children.It suggests that basophils play an important role in the pathogenesis of allergic diseases.Moreover, basophil activation test may have some values in the diagnosis and screening of allergic diseases in children.%目的 探讨嗜碱性粒细胞在儿童过敏性疾病中的临床参考价值.方法 应用流式细胞仪,采用识别CRTH2/CD63/CD4组合抗体,检测过敏性疾病患儿与正常儿童外周血中CRTH2阳性细胞和嗜碱性粒细胞百分比及其活化率,并将检测结果与血清总IgE、特异性IgE、皮肤点刺试验结果作比较,分析其内在联系.结果 68例过

  1. Effect of allergen-specific immunotherapy on recombinant human interleukin 3-mediated amplification of allergen-induced basophil histamine release.

    Science.gov (United States)

    Kowal, Krzysztof; Nolte, Hendrik; Skov, Per Stahl; DuBuske, Lawrence M

    2005-01-01

    Decreased allergen-induced histamine release from peripheral blood basophils in allergic rhinitis patients treated with specific immunotherapy (SIT) correlates with clinical outcomes of SIT. The aim of this study was to investigate if decreased histamine release is a permanent effect of SIT. Fifty-one patients (mean age, 35.3 years) with allergic rhinitis, diagnosed based on clinical history and positive skin-prick test results to common aeroallergens, were studied. Twenty-three patients had never received SIT (group A), and 28 patients had been treated with inhalant allergen extracts (group B). Eleven patients from group A participated in a prospective part of this study. Basophil histamine release in these patients was evaluated before (TO) and after-1 year (TI) of SIT. Histamine release from peripheral blood with and without interleukin (IL)-3 pretreatment was performed using the glass-fiber-based histamine release test. Brief pretreatment of whole blood basophils with one of the four concentrations (0.01, 0.1, 1, or 10 ng/mL) of recombinant human IL(rhIL)-3, rhIL-5, or rh-granulocyte-macrophage colony-stimulating factor resulted in a significant amplification of allergen-induced basophil histamine release. The amplification using cytokines at the optimal concentrations was the greatest with rhIL-3 and the lowest with rhIL-5; therefore, for further studies rhIL-3 was used. Prospective analysis showed no significant difference in allergen-induced basophil histamine release on rhIL-3 pretreatment after 1 year of SIT (192.7 +/- 75.3 ng and 176.1 +/- 76.4 ng for T0 and T1, respectively; p = 0.18). Short-term SIT does not decrease rhIL-3-mediated amplification of allergen-induced histamine release from peripheral blood basophils.

  2. Expression profiling of constitutive mast cells reveals a unique identity within the immune system

    Science.gov (United States)

    Dwyer, Daniel F.; Barrett, Nora A.; Austen, K. Frank

    2016-01-01

    Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity IgE receptor and are implicated in host defense and diverse immune-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. We found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. We observed minimal homology between mast cells and basophils, which share more overlap with other circulating granulocytes than with mast cells. Derivation of mast cell and basophil transcriptional signatures underscores their differential capacity to detect environmental signals and influence the inflammatory milieu. PMID:27135604

  3. Role of protein kinase C in histamine release from human basophils.

    Science.gov (United States)

    Morita, Y; Takaishi, T; Honda, Z; Miyamoto, T

    1988-02-01

    In this study, we investigated the role of calcium and phospholipid-dependent protein kinase (protein kinase C, PKC) in the modulation of histamine release from human basophils. A novel and potent inhibitor of PKC, K-252a, inhibited the release of histamine induced by anti-IgE in a dose-dependent manner with ID50 (the dose required for 50% inhibition of histamine release) of 2.2 x 10(-8) M. Histamine release stimulated with 12-0-tetradecanoyl-phorbol-13-acetate(TPA) was also suppressed by K-252a with maximal inhibition of 48.0 +/- 9.3% at 10(-7) M. In contrast, K-252a did not inhibit the release of histamine in response to FMLP and ionophore A23187. Another inhibitor of PKC, H-7, exhibited a dose-dependent inhibition of anti-IgE-induced histamine release with ID50 of 8.6 x 10(-4) M. H-8 and HA1004, which closely resemble H-7 in chemical structure but are less potent in inhibiting PKC, did not inhibit histamine release stimulated with anti-IgE, but rather enhanced the release at higher concentrations. These results strongly suggest that PKC activation plays a crucial role in the mediation of IgE-mediated histamine release from human basophils.

  4. Diagnostic tests based on human basophils: more potentials and perspectives than pitfalls. II. Technical issues.

    Science.gov (United States)

    De Week, A L; Sanz, M L; Gamboa, P M; Aberer, W; Bienvenu, J; Blanca, M; Demoly, P; Ebo, D G; Mayorga, L; Monneret, G; Sainte Laudy, J

    2008-01-01

    Cellular basophil activation tests (BAT) such as histamine or sulfidoleukotriene-release tests for allergy diagnosis have been available for some time, but expression of basophil-activation markers such as CD63 and CD203c detected by flow cytometry has attracted particular attention in recent years. Not only the potential but also the possible pitfalls of flow-cytometric BAT have been stressed recently. Some authors have suggested that the technical problems are still such that BAT should only be performed in specialist laboratories. In an earlier review based on our clinical experience obtained over several years, we showed that, even using different protocols, reproducible and meaningful clinical results can be obtained. In this paper, we review the current knowledge in relation to several technical issues and show that flow-cytometric BAT already represents a major advance in the field of in vitro allergy diagnosis. We conclude that there are no serious technical justifications for depriving allergic patients of clinically indicated BAT tests, which can be performed reliably by any laboratory with the appropriate experience in allergy diagnosis and flow cytometry.

  5. Diagnostic tests based on human basophils: more potentials and perspectives than pitfalls.

    Science.gov (United States)

    de Weck, A L; Sanz, M L; Gamboa, P M; Aberer, W; Bienvenu, J; Blanca, M; Demoly, P; Ebo, D G; Mayorga, L; Monneret, G; Sainte-Laudy, J

    2008-01-01

    For the diagnosis of allergy, cellular basophil activation tests (BAT), e.g. histamine or sulfidoleukotriene release tests, have long been introduced, but the expression of basophil activation markers such as CD63 and CD203c detected by flow cytometry has attracted more recent attention. A recent opinion paper in this Journal has stressed not only the potential but also the possible pitfalls of flow-cytometric BAT. We have applied clinical validation of various BAT in various ways for several years, and our experience shows that these new technologies have more potentials and perspectives than pitfalls. A comprehensive review of clinically validated studies on allergy to aeroallergens, insect venoms, latex, food allergens and drugs, e.g. myorelaxants, beta-lactams, pyrazolones and non-steroidal anti-inflammatory drugs, as well as chronic urticaria shows clearly that even with different protocols, reproducible and meaningful results can be obtained. Although the available technologies may still be optimized and better standardized, there are no serious reasons to deprive allergic patients of clinically indicated BAT, which can be performed reliably by any laboratory with allergy and flow-cytometric capacity and expertise.

  6. [Basophilic line of the articular cartilage in normal and various pathological states].

    Science.gov (United States)

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance.

  7. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children.

    Science.gov (United States)

    Lanzkowsky, P; Shende, A; Aral, I; Saluja, G

    1975-01-01

    Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients. PMID:1059384

  8. Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia:a case-control study

    Institute of Scientific and Technical Information of China (English)

    Dorina Lauritano; Massimo Petruzzi; Dario Di Stasio; Alberta Lucchese

    2014-01-01

    The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P50.002), duration of mucositis (P50.003) and the average grade of mucositis (P50.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

  9. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  10. The Effects of Herbs and Fruits on Leukaemia

    Directory of Open Access Journals (Sweden)

    Tayebeh Azam Saedi

    2014-01-01

    Full Text Available In developing countries, herbal therapy is the first and basis form of treatment for most types of diseases. About 75–80% of the world’s population prefers herbal therapy as a major treatment due to its better adequacy and satisfactoriness, which enhance human body’s symmetry with minimal side effects. Fruits and plants have been presented from the past as promising tools in becoming a natural anticancer agents. Many of these plant extracts are currently used in cancer therapy and prevention. This review paper will particularly explore and emphasize on herbs and fruits used in the treatment of the leukaemia.

  11. [Characteristic of the yeast isolated from patients with leukaemia].

    Science.gov (United States)

    Fedorovskaia, E A; Rybal'skaia, A P; Skachkova, N K; Mel'nik, E A; Nemirovskaia, L N; Nagornaia, S S; Babich, T V; Polishchuk, L V

    2008-01-01

    It has been shown that biotopes of upper respiratory system and intestine were contaminated with yeast in 44.6% of patients with leukaemia (of 112 examined ones). Their quantity exceeds the boundary value for practically healthy people and is > or = 10(2) KOE/ml in the nasal activity and fauces and leucemia the mycotic complications are mainly caused by anamorphous yeast of ascomycetic affinity. Candida albicans, as well as C. glabrata, C. rugosa and Candida sp. play the leading role. The Candida genus species are mainly sensitive to amphotericine B, clotrisamol and nistatin.

  12. Traffic-related air pollution and risk for leukaemia of an adult population.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Ketzel, Matthias; Harbo Poulsen, Aslak; Sørensen, Mette

    2016-03-01

    Air pollution causes lung cancer, but associations with other cancers have not been established. We investigated whether long-term exposure to traffic-related air pollution is associated with the risk of the general population for leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992-2010 from a nation-wide cancer registry and selected 3,381 control people at random, matched on sex and year of birth, from the entire Danish population. Residential addresses since 1971 were traced in a population registry, and outdoor concentrations of NOx and NO2 , as indicators of traffic-related air pollution, were calculated at each address in a dispersion model. We used conditional logistic regression to estimate the risk for leukaemia after adjustment for income, educational level, cohabitation status and co-morbidity. In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95% confidence interval: 1.04-1.38) per 20 µg/m(3) increase in NOx and 1.31 (1.02-1.68) per 10 µg/m(3) increase in NO2 , calculated as time-weighted average exposure at all addresses since 1971. We found no association with chronic myeloid or lymphocytic leukaemia. This study indicates an association between long-term exposure to traffic-related air pollution and acute myeloid leukaemia in the general population, but not for other subtypes of leukaemia.

  13. Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj

    2006-01-01

    . However, a relationship between the AS status and FcepsilonRI has not been investigated. We aimed to characterize basophils from AS by looking at histamine release (HR) (sensitivity and reactivity) and the FcepsilonRI molecule, and compare it with nonatopic (NA) or allergic (A) persons....

  14. Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection

    DEFF Research Database (Denmark)

    Pinot de Moira, Angela; Fitzsimmons, Colin M; Jones, Frances M;

    2014-01-01

    in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. METHODS: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release...

  15. Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy

    NARCIS (Netherlands)

    Bidad, Katayoon; Nawijn, Martijn C.; van Oosterhout, Antoon J. M.; van der Heide, Sicco; Oude Elberink, Joanne N. G.

    2014-01-01

    Background There is need for an accurate diagnostic test in mastocytosis patients with wasp venom allergy (WVA) and monitoring of these patients during immunotherapy (IT). In this study, we aimed to evaluate sensitivity and specificity of the Basophil Activation Test (BAT) as a diagnostic and monito

  16. Proven/Probable Invasive Fungal Infection in hematologic patients with Acute Myeloid Leukaemia and/or in Allogeneic Hematopoietic Stem Cell Transplant recipients. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available ni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acuta e/o in pazienti co... settimane come terapia di mantenimento per infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia...oietic Stem Cell Transplant recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia... recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acut...ndard con L-AMB 3 mg / kg una volta al giorno nei pazienti ematologici in trattamento per leucemia

  17. Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis

    OpenAIRE

    Williams, Christopher KO; Foroni, Letizia; Luzzatto,Lucio; Saliu, Idris; Levine, Arthur; Greaves, Mel F.

    2014-01-01

    Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt’s lymphoma (BL) are rare in the high-income countries. This report describes clinical and labo...

  18. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    Directory of Open Access Journals (Sweden)

    Nahid Eskandari

    2014-06-01

    Full Text Available Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h or IL-3 (100 ng/ ml, 24 h. Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35 or IL-13 (r=0.47, p=0.098 and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036. There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72 or IL-13 (r=0.162, p=0.5. The reproducibility of cytokines isolated from the same donor (on different occasions indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  19. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    Science.gov (United States)

    Eskandari, Nahid; Bastan, Reza; Ahmadi, Maryam; Peachell, Peter T

    2014-06-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h) or IL-3 (100 ng/ ml, 24 h). Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35) or IL-13 (r=0.47, p=0.098) and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036). There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72) or IL-13 (r=0.162, p=0.5). The reproducibility of cytokines isolated from the same donor (on different occasions) indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  20. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML).

    Science.gov (United States)

    Elbaz, O; Shaltout, A

    2000-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  1. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML); Malignancy.

    Science.gov (United States)

    Elbaz, Osama; Shaltout, Ali

    2001-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  2. Impact of the Functional CD5 Polymorphism A471V on the Response of Chronic Lymphocytic Leukaemia to Conventional Chemotherapy Regimens

    Science.gov (United States)

    Delgado, Julio; Bielig, Torsten; Bonet, Lizette; Carnero-Montoro, Elena; Puente, Xose S.; Colomer, Dolors; Bosch, Elena; Campo, Elias; Lozano, Francisco

    2016-01-01

    Summary The CD5 lymphocyte receptor -a bona fide immunohistochemical marker of chronic lymphocytic leukaemia (CLL) cells- is a negative regulator of activation signals from the antigen-specific B-cell receptor (BCR). Given that signalling components of the BCR are important contributors to the variable clinical behaviour of CLL, the relevance of functional variants of CD5 on CLL prognosis was explored. The results show that germline-encoded CD5 variants influence the survival to conventional chemotherapies from CLL patients with unmutated IGVH genes. This result supports the notion that CD5 is not only a phenotypic marker but a relevant player in CLL cell biology. PMID:26991857

  3. 活化嗜碱粒细胞在变应性鼻炎患者外周血中的表达%Expression of activated basophile in peripheral blood in patients with allergic rhinitis

    Institute of Scientific and Technical Information of China (English)

    张淳; 石嘉俪; 徐雅男; 王利民; 王家东

    2011-01-01

    目的 探讨嗜碱粒细胞在变应性鼻炎患者外周血中数量及活化率的变化及其临床意义.方法 以化学诱导趋向性受体单抗作为特异性的荧光标记,采用三色免疫荧光标记流式细胞术对20例急性发作期变应性鼻炎患者(急性组)、20例反复发作变应性鼻炎患者(慢性组)及30例健康者(对照组)的外周血嗜碱粒细胞及其活化率进行定量检测.结果 慢性组外周血化学诱导趋向性受体及嗜碱粒细胞高于急性组(P<0.01)和对照组(P<0.05),对照组高于急性组(P<0.01).慢性组与急性组嗜碱粒细胞活化率均高于对照组(P<0.01).结论 嗜碱粒细胞活化是导致变应性鼻炎症状出现的主要因素之一.慢性期患者嗜碱粒细胞的持续增高和活化可能与变应性鼻炎反复发作有关.%Objective To evaluate the number and the activation rate of basophile in peripheral blood in patients with allergic rhinitis and their clinical significance. Methods The chemoattractant receptor-homologus molecule expressed on T helper cells was used as a specific fluorescent marker. Twenty patients with acute allergic rhinitis, 20 patients with chronic allergic rhinitis and 30 healthy controls were evaluated the number and the activation rate of basophile in peripheral blood with three-color fluorescent flow cytometry analysis. Results The numbers of chemoattractant receptor-homologus molecule expressed on T helper cells and basophile were significantly larger in chronic allergic rhinitis group than those in acute allergic rhinitis group (P<0. 01) and normal group (P< 0. 05). The activation rate of basophile was significantly higher in acute allergic rhinitis and chronic allergic rhinitis group than that in control group(P<0. 01). Conclusion The activation of basophile is one of the main factors inducing the symptoms of allergic rhinitis. The continuous increase of the number and the activation rate of basophile may be involved in

  4. Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.

    Science.gov (United States)

    Pession, A; Rondelli, R; Basso, G; Rizzari, C; Testi, A M; Fagioli, F; De Stefano, P; Locatelli, F

    2005-12-01

    Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

  5. Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

    Science.gov (United States)

    Sive, J I; Basilico, S; Hannah, R; Kinston, S J; Calero-Nieto, F J; Göttgens, B

    2016-01-01

    Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.

  6. Quality of life, reproduction and sexuality after stem cell transplantation with partially T-cell-depleted grafts and after conditioning with a regimen including total body irradiation.

    NARCIS (Netherlands)

    Claessens, J.J.M.; Beerendonk, C.C.M.; Schattenberg, A.V.M.B.

    2006-01-01

    Thirty-four men and 36 women (median age 43 and 45 years, respectively) underwent stem cell transplantation (SCT) for acute leukaemia in first complete remission or chronic myelogenous leukaemia in first chronic phase between 1981 and 2001 from HLA-identical siblings. The conditioning regimen includ

  7. Characterizing the inhibitory action of zinc oxide nanoparticles on allergic-type mast cell activation.

    Science.gov (United States)

    Feltis, B N; Elbaz, A; Wright, P F A; Mackay, G A; Turney, T W; Lopata, A L

    2015-08-01

    The development of nanoparticles (NPs) for commercial products is undergoing a dramatic expansion. Many sunscreens and cosmetics now use zinc oxide (ZnO) or titania (TiO2) NPs, which are effective ultraviolet (UV) filters. Zinc oxide topical creams are also used in mild anti-inflammatory treatments. In this study we evaluated the effect of size and dispersion state of ZnO and TiO2 NPs, compared to "bulk" ZnO, on mast cell degranulation and viability. ZnO and TiO2 NPs were characterized using dynamic light scattering and disc centrifugation. Rat basophilic leukaemia (RBL-2H3) cells and primary mouse bone marrow-derived mast cells (BMMCs) were exposed to ZnO and TiO2 NPs of different sizes (25-200 nm) and surface coatings at concentrations from 1 to 200 μg/mL. The effect of NPs on immunoglobulin E (IgE)-dependent mast cell degranulation was assessed by measuring release of both β-hexosaminidase and histamine via colorimetric and ELISA assays. The intracellular level of Zn(2+) and Ca(2+) ions were measured using zinquin ethyl ester and Fluo-4 AM fluorescence probes, respectively. Cellular viability was determined using the soluble tetrazolium-based MTS colorimetric assay. Exposure of RBL-2H3 and primary mouse BMMC to ZnO NPs markedly inhibited both histamine and β-hexosaminidase release. This effect was both particle size and dispersion dependent. In contrast, TiO2 NPs did not inhibit the allergic response. These effects were independent of cytotoxicity, which was observed only at high concentrations of ZnO NPs, and was not observed for TiO2 NPs. The inhibitory effects of ZnO NPs on mast cells were inversely proportional to particle size and dispersion status, and thus these NPs may have greater potential than "bulk" zinc in the inhibition of allergic responses.

  8. Birth weight in offspring and leukaemia risk in parents-A nation-wide register-based cohort study from Denmark

    DEFF Research Database (Denmark)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa

    2013-01-01

    Spurred by previous observations we assessed the relationship between offspring birth weight and parental leukaemia risk in a register-based investigation including 2.4 million parents of 2 million Danish children. Regardless of analytical approach, offspring birth weight was not associated...... with parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our...... investigation indicates that offspring birth weight is not strongly associated with parental leukaemia risk....

  9. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I.; Helisch, A.; Bartenstein, P. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Mainz (Germany); Meyer, R.G.; Herr, W. [III. Medizinische Klinik und Poliklinik (Haematologie), Universitaetsklinikum Mainz (Germany)

    2005-07-01

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  10. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  11. [Necrotizing tonsillitis and renal vein thrombosis due to acute myeloid leukaemia].

    Science.gov (United States)

    Akram, Javed; Josefsson, Pernilla; Rømeling, Frans

    2012-09-01

    A 37-year-old woman was admitted to hospital with severe tonsillitis with unilateral necrotizing tonsillitis. She suddenly got fever, malaise, difficulties swallowing, pain in the throat and deterioration despite four days of penicillin treatment. During hospitalisation, she experienced abdominal pain, and blood tests showed pancytopenia. She was transferred to a haematological department, where a bone marrow biopsy showed acute myeloid leukaemia. Subsequently, an abdominal computed tomography with intravenous contrast revealed bilateral renal vein thrombosis, probably because of coagulopathy due to leukaemia.

  12. Nuclear power plants and childhood leukaemia: lessons from the past and future directions.

    Science.gov (United States)

    Kuehni, C; Spycher, B D

    2014-01-01

    In the 1980s, leukaemia clusters were discovered around nuclear fuel reprocessing plants in Sellafield and Dounreay in the United Kingdom. This raised public concern about the risk of childhood leukaemia near nuclear power plants (NPPs). Since then, the topic has been well-studied, but methodological limitations make results difficult to interpret. Our review aims to: (1.) summarise current evidence on the relationship between NPPs and risk of childhood leukaemia, with a focus on the Swiss CANUPIS (Childhood cancer and nuclear power plants in Switzerland) study; (2.) discuss the limitations of previous research; and (3.) suggest directions for future research. There are various reasons that previous studies produced inconclusive results. These include: inadequate study designs and limited statistical power due to the low prevalence of exposure (living near a NPP) and outcome (leukaemia); lack of accurate exposure estimates; limited knowledge of the aetiology of childhood leukaemia, particularly of vulnerable time windows and latent periods; use of residential location at time of diagnosis only and lack of data on address histories; and inability to adjust for potential confounders. We conclude that risk of childhood leukaemia around NPPs should continue to be monitored and that study designs should be improved and standardised. Data should be pooled internationally to increase the statistical power. More research needs to be done on other putative risk factors for childhood cancer such as low-dose ionizing radiation, exposure to certain chemicals and exposure to infections. Studies should be designed to allow examining multiple exposures.

  13. Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Haslam, K

    2012-02-01

    BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.

  14. Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

    Science.gov (United States)

    Spiers, A S; Roberts, P D; Marsh, G W; Parekh, S J; Franklin, A J; Galton, D A; Szur, Z L; Paul, E A; Husband, P; Wiltshaw, E

    1975-12-13

    Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

  15. Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and modulates virus production

    Directory of Open Access Journals (Sweden)

    Koester Mario

    2006-09-01

    Full Text Available Abstract Background Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways. Results The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV at the plasma membrane (PM and the formation of virus like particles in multivesicular bodies (MVBs. In our study we show that caveolin-1 (Cav-1, a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly. Conclusion This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.

  16. The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Alberts Justin C

    2007-10-01

    Full Text Available Abstract Background Colorectal cancer and B cell chronic lymphocytic leukaemia (CLL have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another. Case presentation A 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL. Conclusion Whilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.

  17. A positive serum basophil histamine release assay is a marker for ciclosporin-responsiveness in patients with chronic spontaneous urticaria

    DEFF Research Database (Denmark)

    Iqbal, Kamran; Bhargava, Kapil; Skov, Per Stahl;

    2012-01-01

    ABSTRACT: The electronic records of 398 patients with chronic spontaneous urticaria (CSU) who had had a serum basophil histamine release assay (BHRA) performed as a marker of functional autoantibodies were audited. The BHRA was positive in 105 patients (26.4%). Fifty eight were treated with ciclo...... with ciclosporin because they were H1 anti-histamine unresponsive. CSU patients with a positive BHRA were more likely to respond clinically (P...

  18. Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?

    Directory of Open Access Journals (Sweden)

    Alexopoulos Evangelos C

    2006-07-01

    Full Text Available Abstract Background Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML. Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. Case presentation Two white females (A and B hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5. The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3. Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987–1993 and 1997–2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently

  19. Temporal trends in childhood leukaemia incidence following exposure to radioactive fallout from atmospheric nuclear weapons testing.

    Science.gov (United States)

    Wakeford, Richard; Darby, Sarah C; Murphy, Michael F G

    2010-05-01

    Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that

  20. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  1. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  2. Induction of the pro-myelocytic leukaemia gene by type I and type II interferons

    Directory of Open Access Journals (Sweden)

    M. Heuser

    1998-01-01

    Full Text Available The physiological role of the pro-myelocytic leukaemia (PML gene product is poorly defined. Among other functions, PML is involved in haem atopoietic differentiation and in control of cell growth and tumorigenesis. We investigated the regulation of human PML expression by interferons (IFNs and IL-1 in various human haematopoietic lines (U937, THP1, HL60, NB4, in human diploid fibroblasts and in human peripheral blood leukocytes. Cytokineinduced modulation of PML expression was assessed by Northern blot analyses, flow cytometry studies and in situ immunolabelling. Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner. In situ immunolabelling revealed that upregulation of protein expression by IFN-α is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies. Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PMLproteins observed in inflammatory tissues and in proliferative states.

  3. Clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleucocytosis.

    Science.gov (United States)

    Daver, Naval; Kantarjian, Hagop; Marcucci, Guido; Pierce, Sherry; Brandt, Mark; Dinardo, Courtney; Pemmaraju, Naveen; Garcia-Manero, Guillermo; O'Brien, Susan; Ferrajoli, Alessandra; Verstovsek, Srdan; Popat, Uday; Hosing, Chitra; Anderlini, Paolo; Borthakur, Gautam; Kadia, Tapan; Cortes, Jorge; Ravandi, Farhad

    2015-03-01

    The clinical characteristics, treatment options and outcomes in patients with acute promyelocytic leukaemia (APL) and hyperleucocytosis remain poorly defined. This study reviewed 242 consecutive patients with APL; 29 patients (12%) had a white blood cell count (WBC) ≥ 50 × 10(9) /l at presentation (median WBC 85·5 × 10(9) /l). Patients with hyperleucocytosis had inferior complete remission (CR) rates (69% vs. 88%; P = 0·004) and higher 4-week mortality (24% vs. 9%; P = 0·018) compared to patients without hyperleucocytosis. We noted a trend towards inferior 3-year disease-free survival (DFS) (69% vs. 80%; P = 0·057) and inferior 3-year overall survival (OS) (74% vs. 92%; P = 0·2) for patients with hyperleucocytosis. Leukapheresis was performed in 11 (38%) of the 29 patients with hyperleucocytosis. CR rate and 3-year OS were not significantly improved in patients who received leukapheresis. CR rate and 3-year OS for the 15 patients with hyperleucocytosis treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) plus cytotoxic therapy (idarubicin or gemtuzumab ozogamicin) combinations were 100% and 100% vs. 57% and 35% for the 14 patients treated with non-ATRA/ATO combinations (P = 0·004 and P = 0·002). Leukapheresis does not improve the outcomes in patients with APL presenting with hyperleucocytosis. ATRA/ATO-based combinations are superior to other regimens in these patients.

  4. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

    Science.gov (United States)

    Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C. H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

    2017-01-01

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. PMID:28165464

  5. Has fallout from the Chernobyl accident caused childhood leukaemia in Europe? An update on epidemiologic evidence

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, W. [Bremen Inst. for Prevention Research and Social Medicine (BIPS), Bremen (Germany)

    2001-07-01

    Background: According to radiation risk estimates uniformly adopted by various official organizations, exposure to Chernobyl fallout is unlikely to have caused any measurable health risk in central Europe. Methods and Results: A reevaluation of ECLIS (European Childhood Leukaemia and Lymphoma Incidence Study), a large IARC-coordinated project revealed a slightly higher leukaemia incidence in the most contaminated European regions, and an increasing trend with estimated cumulative excess radiation dose. The excess corresponds to 20 cases of childhood leukaemia in the study area until 1991. Recent evidence from Greece and Germany indicate significantly higher risks in the cohort of children in utero at the time of the initial fallout. In Greece, a positive trend was observed over three regions of increasing average fallout contamination (p=0.005). Conclusion: Chernobyl fallout could well have caused a small, but significant excess of childhood leukaemia cases in Europe. The etiologic mechanism might include an induction of chromosome aberrations in early pregnancy. Increased risks in the birth cohort exposed in utero correspond to 11 excess cases in Greece and another 11.4 excess cases in Germany alone. Exposure misclassification and underascertainment of incident cases render post-Chernobyl risk estimates probably too low. If indeed Chernobyl fallout has caused childhood leukaemia cases in Europe, we would also expect an increased incidence for other childhood cancers and excess malignancies in adults as well as non-malignant diseases of all ages. Neither of these endpoints have as yet been systematically studied. (orig.)

  6. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

  7. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea

    2005-05-01

    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  8. Scrapie strain-specific interactions with endogenous murine leukaemia virus.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Caruso, V; Sersen, E

    1999-01-01

    The finding that a senescence-accelerated mouse (SAMP8) shows early brain ageing, with histopathological changes resembling those seen in scrapie, combined with the discovery of high levels of endogenous murine leukaemia virus (MuLV) in brains of SAMP8 mice prompted us to examine the effect of scrapie infection on MuLV titres in this strain and in one of its progenitors, the AKR strain. Three scrapie strains (ME7, 22L and 139A) that had a comparatively short incubation period in SAMP8 and AKR mice caused an increase in brain MuLV titres that was scrapie strain-specific: in each mouse strain, the greatest effect was with 1 39A, and the least with ME7. The 22A scrapie strain, which has a long incubation period in SAMP8 mice, did not affect MuLV titres in brains of this mouse strain. Previous analyses of scrapie incubation periods in AKR, SAMP8 and another strain derived from an AKR cross (SAMR1) showed an inverse relationship between brain MuLV titres and scrapie incubation periods. This finding, combined with the effect of scrapie on MuLV titres, suggests an interaction between the scrapie infectious process and MuLV replication.

  9. A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

    Directory of Open Access Journals (Sweden)

    Jameel Al-Ghazaly

    2014-12-01

    Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

  10. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  11. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Morgulis Yuri

    2012-05-01

    Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  12. Production of cytokines of type II (IL-4 and IL-13) by basophil polynuclear: effects of chimiokins and stimulation by the diesel particulates; Production de cytokines de type 2 (IL-4 et IL-13) par les polynucleaires basophiles: effects des chimiokines et stimulation par les particules de diesel

    Energy Technology Data Exchange (ETDEWEB)

    Devouassoux, G.

    2000-07-01

    Cytokines of type II are critical factors in the generation of allergic inflammation. There is a correlation between the allergy incidence and the pollutants exposition. The impact of the diesel particles on the allergic response is established but their impact on the basophil is unknown. This study shows that the basophil is a target for the diesel particles, responsible of an important production of IL-4, independent of the clinical status but dependent of the oxidative stress. (A.L.B.)

  13. Outcome of hyperleukocytic adult acute myeloid leukaemia: a single-center retrospective study and review of literature.

    Science.gov (United States)

    Marbello, Laura; Ricci, Francesca; Nosari, Anna Maria; Turrini, Mauro; Nador, Guido; Nichelatti, Michele; Tedeschi, Alessandra; Vismara, Eleonora; Morra, Enrica

    2008-08-01

    Hyperleukocytic acute myeloid leukaemia is considered to have a poor prognosis due to high early death rate secondary to leukostasis. Supportive treatments do not seem to have reduced early exitus in this subset of patients. Prognostic impact of hyperleukocytosis on outcome has been the object of few studies. Clinical characteristics and outcome of 45 consecutive adult patients with newly diagnosed acute myeloid leukaemia presenting to our institution with a white cell count (WBC) above 100 x 10(9)L(-1) were reviewed. The outcome of this subset of patients was compared with 200 patients with a leukocyte count lower than 100 x 10(9)L(-1) similarly treated in the same period. Eight hyperleukocytic patients (17%) died of intracranial haemorrhage or pulmonary failure due to leukostasis within the first 7 days of treatment. A significant association was found between complete response (CR) and absence of hyperleukocytosis, but if early deaths were removed from analysis the difference was no longer significant. Hyperleukocytosis also significantly reduces the overall survival (OS) but does not significantly influence the disease-free survival (DFS). We reviewed in literature studies in which the outcome of series of at least 10 patients with hyperleukocytosis were compared with that of patients with a leukocyte count lower than 100 x 10(9)L(-1). Our data were consistent with those of the literature regarding the rate of early mortality and causes of death. In most of the reviewed series hyperleukocytosis does not seem to influence the outcome of patients. Avoiding early death seems to be an important step in this subset of patients. New data about pathophysiology of leukostasis are needed.

  14. Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat.

    Science.gov (United States)

    Laszlo, Daniele; Agazzi, Alberto; Goldhirsch, Aron; Cinieri, Saverio; Bertolini, Francesco; Rabascio, Cristina; Pruneri, Giancarlo; Calabrese, Liliana; Cocquio, Angela; Martinelli, Giovanni

    2004-04-01

    Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates

  15. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  16. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity.

    Science.gov (United States)

    Jacoby, Elad; Nguyen, Sang M; Fountaine, Thomas J; Welp, Kathryn; Gryder, Berkley; Qin, Haiying; Yang, Yinmeng; Chien, Christopher D; Seif, Alix E; Lei, Haiyan; Song, Young K; Khan, Javed; Lee, Daniel W; Mackall, Crystal L; Gardner, Rebecca A; Jensen, Michael C; Shern, Jack F; Fry, Terry J

    2016-07-27

    Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL.

  17. Detection of transient and persistent feline leukaemia virus infections.

    Science.gov (United States)

    Jarrett, O; Golder, M C; Stewart, M F

    1982-03-01

    A study was made of cats persistently or transiently viraemic with feline leukaemia virus (FeLV) following experimental oronasal infection. Cats of two ages were exposed to the virus. One group was infected when eight weeks old in the expectation that most of the cats would become persistently viraemic, and the second group when 16 weeks old, so that some would show signs of a transient infection and then recover. The periods following infection when virus was detectable in the blood and in the oropharynx were determined for each group. Three methods for detecting viraemia were compared: virus isolation, immunofluorescence on blood smears and an enzyme-linked immunosorbent assay (ELISA). There was good overall agreement among the three tests in detecting virus-positive cats. Virus was found sooner after infection by virus isolation than by the other methods, and virus appeared in the blood slightly sooner in cats which developed persistent viraemia than in transiently viraemic cats. Infectious FeLV was isolated from the oropharynx of all of the persistently viraemic cats, in most cases simultaneously with virus in the plasma. Virus was also isolated from the mouth of most transiently viraemic cats. Under field conditions such transient excretion of virus lasting only a few days would rarely be detected in a single sampling. This might explain how FeLV is maintained in free range urban cats in the absence of a large number of cats with persistent active FeLV infection. For routine diagnosis, immunofluorescence would appear to offer the best chance of differentiating transient and persistent infections by FeLV.

  18. Human herpes virus-6 seroprevalence and leukaemias: a case-control study. GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto).

    Science.gov (United States)

    Gentile, G; Mele, A; Ragona, G; Faggioni, A; Zompetta, C; Tosti, M E; Visani, G; Castelli, G; Pulsoni, A; Monarca, B; Martino, P; Mandelli, F

    1999-06-01

    The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07-1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB.

  19. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B;

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...

  20. Gemtuzumab-induced orchitis in a patient with refractory acute promyelocytic leukaemia.

    Science.gov (United States)

    Jalil-ur-Rehman; Kelta, Muhammad; Awad, Khalid; Beirouti, Basim Al; Nasser, Shahzad; Aslam, Muhammad

    2012-09-01

    We report the case of a 22-year-old Saudi male patient who was treated extensively in the past with various regimens for acute promyelocytic leukaemia that was refractory to all standard treatments. He was ultimately administered Gemtuzumab to induce remission and subjected to an allogeneic bone marrow transplant. However, he developed orchitis, which has not been previously reported with this agent.

  1. Transmission of bovine leukaemia virus within dairy herds by simulation modelling

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but th

  2. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 la

  3. Cost-effectiveness of obinutuzumab for chronic lymphocytic leukaemia in The Netherlands

    NARCIS (Netherlands)

    Blommestein, Hedwig M.; de Groot, Saskia; Aarts, Mieke J.; Vemer, Pepijn; de Vries, Robin; van Abeelen, Annet F. M.; Posthuma, E. F. M. Ward; Uyl-de Groota, Carin A.

    2016-01-01

    Background: Obinutuzumab combined with chlorambucil (GClb) has shown to be superior to rituximab combined with chlorambucil (RClb) and chlorambucil (Clb) in newly diagnosed patients with chronic lymphocytic leukaemia (CLL). This study evaluates the cost-effectiveness per life-year and quality adjust

  4. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Autrup, Judith; Hokland, Peter; Pedersen, Lars;

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GSTM...

  5. Clinical presentation of childhood leukaemia : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Clarke, Rachel T; Van den Bruel, Ann; Bankhead, Clare; Mitchell, Christopher D; Phillips, Bob; Thompson, Matthew J

    2016-01-01

    OBJECTIVE: Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to di

  6. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

  7. Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

    Science.gov (United States)

    Conte, N; Varela, I; Grove, C; Manes, N; Yusa, K; Moreno, T; Segonds-Pichon, A; Bench, A; Gudgin, E; Herman, B; Bolli, N; Ellis, P; Haddad, D; Costeas, P; Rad, R; Scott, M; Huntly, B; Bradley, A; Vassiliou, G S

    2013-09-01

    Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

  8. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    NARCIS (Netherlands)

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  9. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    Science.gov (United States)

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  10. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  11. Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands.

    NARCIS (Netherlands)

    Gorkom, B.A.P. van; Huisman, C.A.; Wijermans, P.W.; Schipperus, M.R.

    2007-01-01

    BACKGROUND: Alemtuzumab (MabCampath) is a monoclonal antibody against CD52, indicated as third-line treatment of chronic lymphocytic leukaemia (CLL). As most important side effect opportunistic infections are mentioned. It is, however, unknown whether these complications often lead to problems in ge

  12. Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity

    Directory of Open Access Journals (Sweden)

    N. Abuaf

    2012-01-01

    Full Text Available Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT and monocyte (MAT activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37% and specificity (90% of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P<0.001 or MAT 10/22 (46%, P<0.01 were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.

  13. Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia.

    Science.gov (United States)

    Ridinger-Saison, M; Evanno, E; Gallais, I; Rimmelé, P; Selimoglu-Buet, D; Sapharikas, E; Moreau-Gachelin, F; Guillouf, C

    2013-09-01

    Deregulation of transcriptional networks contributes to haematopoietic malignancies. The transcription factor Spi-1/PU.1 is a master regulator of haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression inhibits differentiation and promotes resistance to apoptosis in erythroleukaemia. Here, we show that Spi-1 inhibits mitochondrial apoptosis in vitro and in vivo through the transcriptional repression of Bim, a proapoptotic factor. BIM interacts with MCL-1 that behaves as a major player in the survival of the preleukaemic cells. The repression of BIM expression reduces the amount of BIM-MCL-1 complexes, thus increasing the fraction of potentially active antiapoptotic MCL-1. We then demonstrate that Spi-1 represses Bim transcription by binding to the Bim promoter and by promoting the trimethylation of histone 3 on lysine 27 (H3K27me3, a repressive histone mark) on the Bim promoter. The PRC2 repressive complex of Polycomb is directly responsible for the deposit of H3K27me3 mark at the Bim promoter. SUZ12 and the histone methyltransferase EZH2, two PRC2 subunits bind to the Bim promoter at the same location than H3K27me3, distinct of the Spi-1 DNA binding site. As Spi-1 interacts with SUZ12 and EZH2, these results indicate that Spi-1 modulates the activity of PRC2 without directly recruiting the complex to the site of its activity on the chromatin. Our results identify a new mechanism whereby Spi-1 represses transcription and provide mechanistic insights on the antiapoptotic function of a transcription factor mediated by the epigenetic control of gene expression.

  14. Feline leukaemia provirus load during the course of experimental infection and in naturally infected cats.

    Science.gov (United States)

    Hofmann-Lehmann, R; Huder, J B; Gruber, S; Boretti, F; Sigrist, B; Lutz, H

    2001-07-01

    Feline leukaemia virus (FeLV) infection in domestic cats can vary in its outcome (persistent, transient, no infection) for reasons that are not entirely known. It was hypothesized that the initial virus and provirus load could significantly influence the course of retrovirus infection. To determine the role of provirus loads, two methods of PCR, a nested PCR and a fluorogenic probe-based (TaqMan) real-time quantitative PCR, which were specific to the U3 region of FeLV-A were established. FeLV provirus in naturally and experimentally infected cats was then measured. Only 3 weeks after experimental FeLV-A infection, persistently infected cats demonstrated higher provirus loads and lower humoral immune responses than cats that had overcome antigenaemia. Lower initial provirus loads were associated with successful humoral immune responses. Unexpectedly, provirus in the buffy-coat cells of two cats that tested negative for the p27 antigen (a marker for viraemia) was also detected. In 597 Swiss cats, comparison of p27 antigen levels with PCR results revealed broad agreement. However, similar to the experimental situation, a significant number of animals (10%) was negative for the p27 antigen and FeLV-positive by PCR. These cats had a mean provirus load 300-fold lower than that of animals testing positive for the p27 antigen. In conclusion, an association between the provirus load and the outcome of FeLV infection was found. Detection of provirus carriers should contribute to further the control of FeLV. In addition, quantification of provirus loads will lead to a better understanding of FeLV pathogenesis and anti-retrovirus protective mechanisms.

  15. The Polo-Like Kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia.

    Science.gov (United States)

    Casolaro, Alessia; Golay, Josee; Albanese, Clara; Ceruti, Roberta; Patton, Veronica; Cribioli, Sabrina; Pezzoni, Alice; Losa, Marco; Texido, Gemma; Giussani, Ursula; Marchesi, Francesco; Amboldi, Nadia; Valsasina, Barbara; Bungaro, Silvia; Cazzaniga, Gianni; Rambaldi, Alessandro; Introna, Martino; Pesenti, Enrico; Alzani, Rachele

    2013-01-01

    CD56 is expressed in 15-20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+) monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+) AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.

  16. Results of a randomized trial in children with Acute Myeloid Leukaemia : Medical Research Council AML12 trial

    NARCIS (Netherlands)

    Gibson, Brenda E. S.; Webb, David K. H.; Howman, Andrew J.; De Graaf, Siebold S. N.; Harrison, Christine J.; Wheatley, Keith

    2011-01-01

    The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (

  17. Generation and epitope analysis of human monoclonal antibody isotypes with specificity for the timothy grass major allergen Phl p 5a

    DEFF Research Database (Denmark)

    Hecker, J.; Diethers, A.; Seismann, H.;

    2011-01-01

    of the antibodies with the allergen was assessed. Applicability in allergy diagnostics was confirmed by establishment of artificial human sera. Functionality of both antibodies was further demonstrated in receptor binding studies and mediator release assays using humanised rat basophil leukaemia cells (RBL-SX38...

  18. A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation.

    Science.gov (United States)

    Meyer, N Helge; Mayerhofer, Hubert; Tripsianes, Konstantinos; Blindow, Silke; Barths, Daniela; Mewes, Astrid; Weimar, Thomas; Köhli, Thies; Bade, Steffen; Madl, Tobias; Frey, Andreas; Haas, Helmut; Mueller-Dieckmann, Jochen; Sattler, Michael; Schramm, Gabriele

    2015-09-04

    The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism.

  19. Flow cytometric analysis of the inhibition of human basophil activation by histamine high dilutions – a replication study

    Directory of Open Access Journals (Sweden)

    Chantal Wälchli

    2012-09-01

    Full Text Available Background: Inhibition of human basophil activation by highly diluted histamine was reported to be a reliable experimental model to examine biological effects of high dilutions. However, independent replications did not always yield concordant results. Aims: We aimed at performing an independent replication of a former study [1] using rigorously controlled experimental conditions to minimise confounding factors. Materials and Methods: In 20 independent experiments, human basophils were treated with highly diluted histamine (15cH, 16cH, corresponding to 10-30-10-32 M prior to activation by fMLP (formyl-methionyl-leucyl-phenylalanine peptide. Controls were treated with analogously diluted water (15cH, 16cH. The dilutions were prepared freshly for each experiment in deionised water by successive steps of centesimal dilution and agitation (10 s vortex at high speed. Highly diluted samples were blinded and randomised. All samples were set in triplicates. Activated basophils were determined by flow cytometry using anti-CD203c. 20 independent systematic negative control (SNC experiments were carried out to investigate possible systematic errors. Results: No difference in basophil activation was observed between the highly diluted histamine samples and the highly diluted water controls. There was no evidence for a blood donor specificity of the results. The SNC experiments demonstrated the stability of the test system. Experimental variability within and between experiments was slightly reduced for the highly diluted histamine samples. Discussion: This study was designed as an independent reproduction of a former study [1]. Though we strictly adopted the experimental procedure described in [1], our results do not confirm the large inhibitory effects observed for histamine 15cH and 16cH. This lack of reproducibility might be due to minor differences in the experimental design, such as blinding and randomising of the samples, which we chose to

  20. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R; Liu, Wei; Glass, John O; Ji, Qing; Ogg, Robert J; Sabin, Noah D; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Reddick, Wilburn E

    2014-11-01

    Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in

  1. Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

    Science.gov (United States)

    Pinot de Moira, Angela; Fitzsimmons, Colin M.; Jones, Frances M.; Wilson, Shona; Cahen, Pierre; Tukahebwa, Edridah; Mpairwe, Harriet; Mwatha, Joseph K.; Bethony, Jeffrey M.; Skov, Per S.; Kabatereine, Narcis B.; Dunne, David W.

    2014-01-01

    Background. The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. Results. Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy. Conclusions. Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy. PMID:24782451

  2. Detection of residual bcr/abl translocation by polymerase chain reaction in chronic myeloid leukaemia patients after bone-marrow transplantation.

    Science.gov (United States)

    Gabert, J; Thuret, I; Lafage, M; Carcassonne, Y; Maraninchi, D; Mannoni, P

    1989-11-11

    The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/abl hybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abl transcript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

  3. Flow Cytometric Determination of the Expression of gp 51 Protein of Bovine Leukaemia Virus in Experimentally Infected Sheep

    Directory of Open Access Journals (Sweden)

    Szczotka Maria

    2014-10-01

    Full Text Available The study was performed on lambs experimentally infected with bovine leukaemia virus (BLV. The presence of BLV antibodies in sera of infected animals was detected by agar gel immunodiffusion test and ELISA. Proviral DNA was detected by PCR and nested PCR. Dual-colour flow cytometry analysis was performed with the use of specific monoclonal antibodies against lymphocyte CD markers and gp51 viral envelope protein, followed by incubation with fluorescent-labelled secondary antibodies conjugated with FITC or PE. Gp51 viral envelope protein was detected in tumours caused by BLV infection. The BLV infection resulted in depletion of CD4+ lymphocytes, increase in CD8+ lymphocytes, and decrease in CD4+ to CD8+ ratio in infected sheep. Proliferation of IgM+ CD19+ cells was also detected. These cells had an immature character without tendency to differentiate, and their vitality was prolonged. Flow cytometry enabled detection of gp51 expression in sheep blood lymphocytes at the early stages of the infection, before detection of serum antibodies using ELISA.

  4. Epigenetic Guardian: A Review of the DNA Methyltransferase DNMT3A in Acute Myeloid Leukaemia and Clonal Haematopoiesis

    Science.gov (United States)

    Chaudry, Sabah F.

    2017-01-01

    Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific “founder” mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP. PMID:28286768

  5. Acute sinusitis and blindness as the first presentation of chronic lymphocytic leukaemia.

    Science.gov (United States)

    Lim, K H; Thomas, G; van Beers, E J; Hosman, A E; Mourits, M P; van Noesel, C J M; Kater, A P; Reinartz, S M

    2014-12-01

    Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among adults in the Western world, presenting at a median age of 65 years. The diagnosis is usually made incidentally during routine blood examination while the disease is still in its early phase. We report a case of blindness of 24 hours due to acute sinusitis based on CLL localisation in a patient with undiagnosed CLL. Emergency endoscopic sinus surgery and intra- and extra-ocular orbital decompression were performed. The sinusitis resolved after surgery and intravenous antibiotics. Her vision improved within 24 hours and eventually recovered completely after six months. Her CLL remained in an indolent state, needing no active treatment. This case illustrates that blindness from a lymphoproliferative disorder may be treated with emergency endoscopic sinus surgery instead of conventional chemotherapy in order to salvage the vision first, even if the vision is lost for more than 24 hours.

  6. Combination chemotherapy for marrow relapse in children and adolescents with acute lymphocytic leukaemia.

    Science.gov (United States)

    Amadori, S; Spiriti, M A; Meloni, G; Pacilli, L; Papa, G; Mandelli, F

    1981-04-01

    38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37-260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.

  7. Chronic lymphocytic leukaemia: contemporary conceptions of etiology, pathogenesis and peculiarities of clinical manifestations (review

    Directory of Open Access Journals (Sweden)

    Chesnokova N.P.

    2011-06-01

    Full Text Available The research work presents an analysis of literature review and results of investigations on the problems of etiology, pathogenesis, classification and peculiarities of clinical manifestations of chronic lymphocytic leukaemia. Special attention is paid to both contemporary conceptions of carcinogenesis, reflecting the role of proto-oncogenes activation, an-tioncogenes and apoptosis genes suppression in mechanisms of neoplasia development and «specific mechanisms» of oncogenic transformation induction of B-lymphocytes and the subsequent development of the stages of promotion, progression and marked clinical manifestations of formation. Possibility of further improvement of use of immune phe-notype character and oncomarkers in diagnostics of chronic lymphocytic leukaemia clinical variants and in evaluation of effectiveness of its therapy has been indicated in the article

  8. CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies.

    Science.gov (United States)

    Romanski, Annette; Uherek, Christoph; Bug, Gesine; Seifried, Erhard; Klingemann, Hans; Wels, Winfried S; Ottmann, Oliver G; Tonn, Torsten

    2016-07-01

    Many B-cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK-92 cells, a continuously growing NK cell line, showing that anti-CD19-CAR (αCD19-CAR) engineered NK-92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK-92 cells. The 'first generation' CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3ζ chain and a Myc-tag and cloned into a retrovirus backbone. No difference in cytotoxic activity of NK-92 and transduced αCD19-CAR NK-92 cells towards CD19 negative targets was found. However, αCD19-CAR NK-92 cells specifically and efficiently lysed CD19 expressing B-precursor leukaemia cell lines as well as lymphoblasts from leukaemia patients. Since NK-92 cells can be easily expanded to clinical grade numbers under current Good Manufactoring Practice (cGMP) conditions and its safety has been documented in several phase I clinical studies, treatment with CAR modified NK-92 should be considered a treatment option for patients with lymphoid malignancies.

  9. Nucleophosmin mutation analysis in acute myeloid leukaemia: Immunohistochemistry as a surrogate for molecular techniques

    OpenAIRE

    Anita Chopra; Sushant Soni; Haraprasad Pati; Dev Kumar; Rahul Diwedi; Deepak Verma; Garima Vishwakama; Sameer Bakhshi; Suman Kumar; Ajay Gogia; Rajive Kumar

    2016-01-01

    Background & objectives: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple...

  10. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    OpenAIRE

    Monti, G.E.; Frankena, K.; Jong, de, F.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 lactating cows. Time-interval parameters were analysed using a parametric survival model with shared frailty, time until infection was analysed using a Bayesian interval-censoring survival model and ...

  11. Transmission of bovine leukaemia virus within dairy herds by simulation modelling

    OpenAIRE

    Monti, G.E.; Frankena, K.; Jong, de, F.

    2007-01-01

    In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but there is scarce quantitative information of the transmission of BLV in cattle herds. This information is a prerequisite to develop effective BLV control strategies. Mathematical modelling offers ways...

  12. Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS)

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, Bernd

    2015-07-01

    Since July 2015 the study ''ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS) - an international cohort study'' is available. INWORKS comprised data from 300.000 occupational exposed and dosimetric monitored persons from France, USA and UK. The contribution is a critical discussion of this study with respect to the conclusion of a strong evidence of positive associations between protracted low-dose irradiation exposure and leukemia.

  13. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  14. COAGULATION PROFILE IN PATIENTS PRESENTING WITH MALIGNANCIES WITH SPECIAL REFERENCES TO HEAD AND NECK EPITHELIAL CANCERS, LEUKAEMIAS AND LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    Kaberee Bhuyan

    2016-04-01

    Full Text Available BACKGROUND Cancer can cause activation of coagulation in many ways and there is definite evidence of abnormalities in haemostatic mechanism which is seen by the presence of one or more circulating markers of haemostatic activation & this is found to be potentiated by the release of tissue factors or procoagulants from normal tissue destructions during tumour development. OBJECTIVES • To evaluate the range of different types of haemostatic abnormalities in haematological and epithelial malignancies, especially the head and neck epithelial malignancies. • To look for the differences in the grades of these abnormalities in metastatic & non-metastatic malignancies. • To understand the prognostic value of routine tests of coagulation while predicting the outcome of the patient. • MATERIALS AND METHODS The study was conducted in the Department of Pathology, Gauhati Medical College & Hospital, Guwahati from July 2004 to June 2005. 70 cases comprising of head and neck epithelial malignancies, leukaemias and lymphomas without clinical presentation of haemorrhage or thrombosis were selected and coagulation profiles were seen. RESULTS AND OBSERVATION Out of 70 cases of both sexes & different age groups prior to therapeutic intervention, metastatic cases were 22, non-metastatic cases were 29, and 19 cases belonged to leukaemias and lymphomas. The commonest age group affected was 51–60 yrs. and male: female was 3.7: 1. The most frequent abnormality was 41 cases (58.57% of FDP positivity in the serum followed by 36 cases (51.43% of hyperfibrinogenaemia; 32 cases (45.71% shortened bleeding time, etc. DISCUSSION Activated coagulation in cancer leads to increased fibrin deposition stimulated by the destroyed tissues; increased FDPs being a strong marker of coagulation and fibrinolytic activation; increased platelet aggregation by the micro vesicles shed by tumour cells; prolonged PT & APTT being well known markers for disseminated intravascular

  15. The 1957 MRC report on leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Peter G [London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT (United Kingdom)

    2007-12-15

    The estimation of the carcinogenic effects of exposure to low doses of ionizing radiation has depended primarily on extrapolation from effects seen in two populations exposed to relatively high doses-the survivors of the atomic bomb explosions in Japan and patients treated in the UK with x-rays for the arthritic condition ankylosing spondylitis. The study of the leukaemia risk in over 14000 irradiated spondylitis patients was completed in an astonishingly short period of time in the mid-1950s. The full report of the original study has been difficult to access because it was not published in a journal but only as a Special Report of the UK Medical Research Council. To mark 50 years since this publication this full report is reproduced in this issue of the Journal. This accompanying review describes the background to the study, the principal findings and the further follow-up of the population that documented the risks of cancers in addition to leukaemia associated with the x-ray treatment. The architects of the study were a radiobiologist, Michael Court-Brown, and an epidemiologist, Richard Doll. Their very productive study of the leukaemia risk among spondylitics spawned a lifelong collaboration including further seminal studies of the carcinogenic effects of radiation exposure, which are also summarised in the review. (review)

  16. Breaking bad news--parents' experience of learning that their child has leukaemia.

    LENUS (Irish Health Repository)

    Oshea, J

    2012-02-03

    This study aimed to seek parents\\' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.

  17. The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses

    DEFF Research Database (Denmark)

    Blom, Lars H; Martel, Britta C; Larsen, Lau F

    2017-01-01

    BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim...... and ILC2 cells and basophils. In peanut-allergic subjects the peanut-specific Th2 (CD154(+) CRTh2(+) ) cells expressed more CD200R than the non-allergen specific Th2 (CD154(-) CRTh2(+) ) cells. Moreover, co-staining of CD161 and CD200R identified peanut-specific highly differentiated IL-4(+) IL-5(+) Th2...

  18. Pharm GKB: Leukemia, B-Cell, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available UTR Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym Acute... B-Cell Leukemia; Acute B-Cell Leukemias; Acute B-Lymphocytic Leukemia; Acute... B-Lymphocytic Leukemias; Acute lymphoblastic leukaemia, Burkitt's type; Acute lymphoblastic leuka...emia, mature B-cell type; Acute lymphoblastic leukemia, Burkitt's type; Acute lymphoblastic leukemia, mature... B-cell type; B Cell Leukemia, Acute; B Lymphocytic Leukemia, Acute; B-ALL; B-Cell Leukemia, Acute

  19. Mast cells & Company

    Directory of Open Access Journals (Sweden)

    Friederike eJönsson

    2012-02-01

    Full Text Available Classically, allergy depends on IgE antibodies and on high-affinity IgE receptors expressed by mast cells and basophils. This long accepted IgE/FcεRI/mast cell paradigm, on which the definition of immediate hypersensitivity was based in the Gell and Coomb’s classification, appears too reductionist. Recently accumulated evidence indeed requires that not only IgE but also IgG antibodies, that not only FcεRI but also FcγR of the different types, that not only mast cells and basophils but also neutrophils, monocytes, macrophages, eosinophils, and other myeloid cells by considered as important players in allergy. This view markedly changes our understanding of allergic diseases and, possibly, their treatment.

  20. Empirical caspofungin therapy in clinical practice for suspected invasive fungal disease in adults with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Kiehl, Michael G; Egerer, Gerlinde; Engelhardt, Monika; Gross, Barbara

    2015-02-01

    Patients with acute lymphoblastic leukaemia (ALL) after cytotoxic chemotherapy or haematopoietic stem cell transplantation (HSCT) are at risk for life-threatening invasive fungal disease (IFD). The aim was to evaluate the characteristics, antifungal therapy and outcome of adult patients with ALL after chemotherapy or HSCT receiving caspofungin empirically in a clinical setting. Retrospective chart reviews were conducted at nine large tertiary care centres in Germany. Adult patients with ALL treated empirically with caspofungin according to the product label between 2006 and 2012 were eligible. Data were extracted as case reports. In total, 25 patients (12 males, 13 females; median age 37 years; 19 with B-ALL, 6 with T-ALL) with 28 treatment episodes because of suspected IFD (18 episodes after chemotherapy, 10 episodes after allogeneic HSCT) were included in the analysis. Empirical caspofungin therapy (median duration: 19 days, range 1-105 days) was given as first-line monotherapy in 20 (71.4%), second-line monotherapy in five (17.9%) and combination therapy in three (10.7%) episodes respectively. Therapy rated successful according to the physician's overall assessment (inflammatory parameters, clinical symptoms): 20 (95%) of 21 evaluable episodes with therapy duration of at least 8 days. Empirical caspofungin appears to be an effective therapeutic option in critically ill adult ALL patients with suspected IFD in clinical practice.

  1. Leukaemia incidence and survival in children and adolescents in Europe during 1978-1997. Report from the Automated Childhood Cancer Information System project

    NARCIS (Netherlands)

    Coebergh, J. W. W.; Reedijk, A. M. J.; de Vries, E.; Martos, C.; Jakab, Z.; Steliarova-Foucher, E.; Kamps, W. A.

    2006-01-01

    Leukaemias constitute approximately one-third of cancers in children (age 0-14 years) and 10% in adolescents (age 15-19 years). Geographical patterns (1988-1997) and time trends (1978-1997) of incidence and survival from leukaemias in children (n = 29,239) and adolescents (n = 1929) were derived fro

  2. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  3. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    NARCIS (Netherlands)

    Balgobind, B.V.; Hollink, I.H.; Reinhardt, D.; Wering, E.R. van; Graaf, S.S.N. de; Baruchel, A.; Stary, J.; Beverloo, H.B.; Greef, G.E. de; Pieters, R.; Zwaan, C.M.; Heuvel-Eibrink, M.M. van den

    2010-01-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies i

  4. Reversible alterations in epithelial cell turnover in digestive gland of winkles (Littorina littorea) exposed to cadmium and their implications for biomarker measurements.

    Science.gov (United States)

    Zaldibar, B; Cancio, I; Marigómez, I

    2007-02-28

    In marine molluscs, the epithelium of the digestive gland is composed of two cell types, namely, digestive and basophilic cells. Under normal physiological conditions digestive cells outnumber basophilic cells, but under different stress situations the composition of the epithelium changes, basophilic cells apparently replace digestive cell. Winkles, Littorina littorea, were exposed to 1.25mg/l Cd for 20 days to provoke cell type replacement. Then, animals were depurated in clean seawater for 10 days to determine whether cell type replacement was reversible. Digestive glands were fixed in Carnoy and paraffin embedded for histological analysis. The volume densities of basophilic cells (Vv(BAS)) and digestive cells (Vv(DIG)) were calculated by stereology on hematoxylin-eosin stained sections. Vv(BAS) increased and Vv(DIG) decreased in Cd-exposed animals. After estimation of cell size and absolute cell numbers, these changes were attributed to digestive cell loss and concomitant basophilic cell hypertrophy but not to increased numbers of basophilic cells. Cell type composition and cell size almost fully returned to normal values after 10-day depuration. Accordingly, PCNA immunohistochemistry demonstrated that proliferating digestive cells were more abundant in winkles exposed to Cd and after 10-day depuration than in control specimens, suggesting that net digestive cell loss was accompanied by increased digestive cell proliferation. Thus, Cd-exposure seems to provoke an enhanced digestive cell turnover in order to cope with Cd detoxification. Intralysosomal accumulation of metals (autometallographied black silver deposits; BSD) was used as a biomarker of exposure to Cd and lysosomal structural changes as an effect biomarker to see whether cell type composition might have any effect on these endpoints. BSD formed around Cd ions, in digestive cell lysosomes of Cd-exposed winkles whereas basophilic cells appeared devoid of them. After depuration, BSD were less

  5. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils.

    Science.gov (United States)

    Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-02-01

    Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  6. Child leukaemia and low frequency electromagnetic fields; Les leucemies de l'enfant et les champs electromagnetiques basse frequence

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, J.

    2009-07-01

    The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

  7. PCR-based clonality assessment in patients with lymphocytic leukaemias: a single-institution experience

    Indian Academy of Sciences (India)

    Bojana M. Cikota; Ljiljana J. Tukić; Olivera T. Tarabar; Dragana T. Stamatović; Marija N. Elez; Zvonko M. Magić

    2009-12-01

    PCR-based clonality testing can be performed in all lymphoproliferations by analysing gene rearrangements of antigen receptors, rearrangements that are unique for each kind of lymphocyte. Reactive lymphoproliferations have polyclonally rearranged Ig/TCR genes, whereas malignant proliferations (leukaemias and lymphomas) show clonal rearrangements. The aim of this study was to assess the clinical benefits of clonality testing with previously evaluated consensus primers in leukaemia patients. The study included peripheral blood and bone marrow samples of 67 leukaemia patients (32 B-CLL, 24 B-ALL and 11 T-ALL). Clonality testing was based on PCR amplification of rearranged I$_{\\text{gH}}$ and TCR genes. During diagnosis, monoclonal pattern was found in all analysed B-CLL and T-ALL samples. Testing in B-ALL patients showed positive results in all bone marrow and one peripheral blood samples. Results of clonality testing in B-CLL patients during follow-up were concordant between peripheral blood and bone marrow. Obtained results corresponded to clinical course in all but one patient. In B-ALL group, results of molecular testing in peripheral blood and bone marrow confirmed remission estimated according to clinical criteria in all except one patient. Before any clinical sign of relapse, monoclonal pattern was found in six/seven patients by bone marrow and in three/seven patients by peripheral blood analysis, respectively. Results of molecular monitoring in T-ALL patients did not confirme clinical evaluation in two patients. Obtained results indicate high accuracy of re-evaluated primers for clonality assessment in ALL and CLL patients at the time of diagnosis. Results of clonality testing in B-ALL patients indicate that bone marrow analysis has higher sensitivity compared to analysis of peripheral blood.

  8. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  9. Incidence trends and ethnic patterns for childhood leukaemia in Hawaii: 1960-1984.

    OpenAIRE

    Goodman, M. T.; Yoshizawa, C. N.; Kolonel, L. N.

    1989-01-01

    We analysed data obtained from the Hawaii Tumor Registry, a population-based participant in the Surveillance, Epidemiology, and End Results (SEER) programme that monitors cancer incidence and mortality for the entire state. A total of 138 males and 116 females, under the age of 15, were diagnosed with leukaemia between 1960 and 1984, with average annual age-adjusted incidence rates of 49.6 and 44.8 per million, respectively. Time trend analysis by 5-year calendar periods revealed an increasin...

  10. Acute myeloid leukaemia presenting as bilateral proptosis in a young child

    Directory of Open Access Journals (Sweden)

    Charudutt Kalamkar

    2016-06-01

    Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

  11. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate.

    Science.gov (United States)

    Porcu, P; Danielson, C F; Orazi, A; Heerema, N A; Gabig, T G; McCarthy, L J

    1997-08-01

    The clinical and laboratory data of 48 leukapheresis-treated patients with hyperleucocytic leukaemia (HL) was reviewed to assess the correlation between the degree of leucoreduction and early mortality. Leukapheresis resulted in > 50% leucoreductions and postapheresis WBC counts < 100 x 10(9)/l in most patients (64.5%). Patients presenting with neurological, respiratory or renal complications had higher early mortality rates than patients without such complications, despite similar initial WBC counts and comparable leucoreductions. Thus, in these patients, more efficient leucoreduction was not associated with improved early survival.

  12. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

  13. Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

    Full Text Available Background: The incidence of different malignancies is increasing among the world populations. Acute lymphoblastic leukaemia (ALL is the most common of all the paediatric malignancies. Response to induction therapy is one of the most important predictors of long term outcome of ALL. Objective: To see the immediate outcome of paediatric ALL patients following induction therapy. Materials and Methods: This retrospective study was conducted from January 2013 to December 2015. Total 221 paediatric ALL patients were included in this study. Diagnosis was based on history, examination, blast cells count on peripheral blood film and bone marrow study, CSF study and immunophenotyping of peripheral blood/bone marrow aspirate in patients who were financially capable. Among them, parents of 40 (18% patients did not agree to start chemotherapy. According to Modified UK ALL 2003 protocol (Regimen A & B 181 patients were given induction therapy (vincristine, prednisolone, L-asparaginase, and daunomycin in high risk patients. Among them 14 patients discontinued, 10 patients died during chemotherapy and rest 157 patients completed induction phase. Bone marrow study was repeated after completion of induction therapy and remission pattern was seen. Results: Out of 157 chemotherapy completed patients, 137 (87% went into complete remission (25% blast cells in the bone marrow. Ten (5.5% patients died due to bleeding, febrile neutropenia and sepsis during the course of induction therapy. Conclusion: ALL in children is curable with effective chemotherapy. Poverty, ignorance and misconception regarding outcome are responsible for refusal and discontinuation of chemotherapy in third world countries like Bangladesh. Mortality and treatment cost can be reduced with the improvement of the facilities for isolation, barrier nursing and supportive treatment, and by creating awareness.

  14. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

  15. Chronic lymphocytic leukaemia: clinical-aetiological findings in 66 patients and their families

    Directory of Open Access Journals (Sweden)

    Weber Walter

    2007-12-01

    Full Text Available Abstract Background Little is known about the aetiology of chronic lymphocytic leukaemia (CLL. The family medical history is a "genomic tool" capturing interactions of genetic susceptibility, shared environment and common behaviours. Methods A cohort of 66 consecutives patients with CLL (probands was studied in a medical oncology practice (W.W. from 1981 until 2005. A German version of the NCI medical history questionnaire for cancer aetiology was used. Familial clustering analysis was done by comparing the proportion of specific tumours in the first degree relatives of the CLL practice cohort with corresponding proportions of population-based cancer registry data. Results 18 (41% male and 5 (23% female CLL probands had multiple malignancies, e.g. 2 meningiomas, 7 and 19 years after diagnosis of CLL. 46 (12% first degree relatives had malignancies with an excess of CLL. Other conspicuous familial associations are CLL with malignancies of the upper GI tract (oesophagus, stomach and of the nervous system. Conclusion 1. Chronic lymphocytic leukaemia clusters in some families like any other disease. Predisposition genes should be searched. 2. Cancer prevention and early detection should be continued in CLL patients because of their longevity and high risk for multiple malignancies. 3. The overrepresentation of upper GI malignancies in first degree relatives of CLL patients calls for targeted oesophago-gastroscopy screening studies.

  16. [Detection of bovine leukaemia virus (BLV) in tissue samples of naturally and experimentally infected cattle].

    Science.gov (United States)

    Teifke, Jens P; Vahlenkamp, Thomas W

    2008-01-01

    Enzootic bovine leukaemia (EBL) which is caused by the bovine leukaemia virus (BLV) still plays a remarkable role despite a significant success in sanitation programmes. In the Federal Republic of Germany it was not possible to eradicate the disease until today. Sporadically during slaughter or necropsy of cattle neoplastic lesions of the lymphatic tissues are observed that need to be clarified with regard to BLV as etiological agent. Due to the fact that in most instances no serological data are available from the respective animals and blood drawings from the original holdings are not easy to obtain the polymerase chain reaction (PCR) opens new avenues as supplementary diagnostic tool to test unfixed lymphatic tissues for the presence of BLV proviral DNA. Lymph node tissues from 10 naturally or experimentally BLV-infected cattle, which have been monitored virologically and serologically, and tissues from 4 negative animals were processed, DNA was extracted and subjected to PCR to amplify BLV env gene specific sequences. The results show that in cattle with BLV-induced leukosis as well as in cattle, which were clinically healthy and unsuspicious at slaughter or at post-mortem, either with persistent lymphocytosis (PL) or without, BLV proviral DNA could be detected easily in samples of lymphatic tissues and in high concordance with serological data. In this article data from the National and OIE reference laboratory for EBL at the Friedrich-Loeffler-Institut (FLI, Germany) are presented. Elaborated laboratory protocols for processing of tissue samples and performing of BLV-PCR are recommended.

  17. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cowan-Jacob, Sandra W., E-mail: sandra.jacob@novartis.com; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W. [Novartis Institutes for Biomedical Research, Basel (Switzerland)

    2007-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.

  18. A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S; Gelb, L; Galasso, G; Borkowsky, W; LaRussa, P; Ferrara, A

    1985-01-01

    Two hundred forty children with acute leukaemia in remission for at least 1 year were immunized with live attenuated varicella vaccine. All were susceptible to varicella before immunization. There was a seroconversion to varicella-zoster virus in approximately 85% after 1 dose, and in 97% after 2 doses. The major side effect was mild to moderate rash, seen mainly in children with maintenance chemotherapy suspended for 1 week before and 1 week after vaccination. Vaccinees with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact. Twenty-nine vaccinees were subsequently exposed to varicella in their households. The attack rate of clinical varicella in these vaccinees was 21%, which is significantly lower than the 80%-90% attack rate occurring in varicella susceptibles after household exposure. All these breakthrough cases of varicella were mild, even in leukaemics receiving chemotherapy. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukaemia and completely effective in preventing severe varicella in this high-risk group.

  19. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

    Science.gov (United States)

    Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

    2012-01-01

    Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

  20. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  1. Prevention of infection in children with acute leukaemia - No major difference between total and selective bowel decontamination

    NARCIS (Netherlands)

    Muis, N; Kamps, WA

    1996-01-01

    To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non

  2. Central line-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myeloid leukaemia in Piraeus, Greece.

    Science.gov (United States)

    Christakis, G B; Perlorentzou, S; Alexaki, P; Megalakaki, A; Zarkadis, I K

    2006-08-01

    A case of central venous catheter-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myelogenous leukaemia is reported. The patient was successfully treated with amikacin and piperacillin-tazobactam. The clinical isolate was identified as R. mucosa by 16S rRNA gene sequencing.

  3. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Thomsen, C; Sørensen, P G; Karle, H;

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla...

  4. Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

    NARCIS (Netherlands)

    Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

    2001-01-01

    The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

  5. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal;

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...

  6. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

    DEFF Research Database (Denmark)

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

    2015-01-01

    BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...

  7. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  8. The N-terminus of murine leukaemia virus p12 protein is required for mature core stability.

    Directory of Open Access Journals (Sweden)

    Darren J Wight

    2014-10-01

    Full Text Available The murine leukaemia virus (MLV gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices.

  9. The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability

    Science.gov (United States)

    Wight, Darren J.; Boucherit, Virginie C.; Wanaguru, Madushi; Elis, Efrat; Hirst, Elizabeth M. A.; Li, Wilson; Ehrlich, Marcelo; Bacharach, Eran; Bishop, Kate N.

    2014-01-01

    The murine leukaemia virus (MLV) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices. PMID:25356837

  10. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Romero, Adela, E-mail: adela@unam.mx; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira [Universidad Nacional Autónoma de México, Circuito Exterior, CU, 04310 Coyoacán, DF (Mexico); Palomares, Laura A. [Universidad Nacional Autónoma de México, Apartado Postal 510-3, 62250 Cuernavaca, MOR (Mexico); Muñoz-Cruz, Samira; Yépez-Mulia, Lilian [Centro Médico Nacional Siglo XXI, IMSS, Avenida Cuauhtémoc 330, Colonia Doctores, Mexico, DF (Mexico); Orozco-Martínez, Socorro [Instituto Nacional de Pediatría, Insurgentes Sur 3700C, 04530 Cuicuilco, DF (Mexico); Universidad Nacional Autónoma de México, Circuito Exterior, CU, 04310 Coyoacán, DF (Mexico)

    2014-02-01

    This study describes the three-dimensional structure of the endogenous glycosylated allergen Hev b 2 (endo-β-1,3-glucanase), which exhibits three post-translational modifications that form a patch on the surface of the molecule that is proposed to be an allergenic IgE epitope. Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  11. Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils

    Energy Technology Data Exchange (ETDEWEB)

    MacGlashan, D.W. Jr.; Dembo, M.; Goldstein, B.

    1985-12-01

    Recent mathematical models of bivalent hapten-induced histamine release from basophils predict that under appropriate conditions histamine release is maximum when cross-link formation is maximum, at a hapten concentration equal to 1/(2K/sub a/), where K/sub a/ is the average affinity constant of the hapten for a single IgE binding site. To test this prediction the authors sensitized human basophils with a monoclonal anti-dinitrophenol IgE and generated histamine release dose-response curves with a bivalent hapten, ..cap alpha..,epsilon-DNP-lysine. The monoclonal IgE has a published affinity constant of 7.1 x 10/sup 7/ M/sup -1/ for epsilon-DNP-lysine as determined by equilibrium dialysis. From the position of the maximum of the histamine dose-response curves, both in the presence and in the absence of monovalent DNP hapten, the authors determine that the sensitizing IgE has an intrinsic affinity constant of 6.9 +/- 0.5 x 10/sup 7/ M/sup -1/ for such that-DNP-lysine and 1.2 +/- 0.6 x 10/sup 6/ M/sup -1/ for ..cap alpha..-DNP-lysine. The agreement between the two estimates of the epsilon-DNP-lysine affinity constant, one from histamine release experiments involving surface bound IgE and one from binding experiments involving IgE free in solution, 1) is consistent with a central prediction of the theory of cross-linking and 2) indicates that the hapten-binding properties of the IgE are unaffected by its being bound to Fc/sub epsilon/ receptors on the basophil surface. 30 references, 3 figures, 3 tables.

  12. Histamine release from basophil leukocytes in asthma patients after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents

    DEFF Research Database (Denmark)

    Guldager, H; Søndergaard, I

    1987-01-01

    Basophil histamine release is a relatively new investigation technique, which can be used in the diagnosis of anaphylactoid reactions. Our aim in this investigation was to determine reference values for asthma patients and normal subjects. Blood from eight asthmatic patients and eight normal...... subjects was tested for histamine release after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents. There was significantly higher histamine release for asthmatic patients than for normal subjects, P less than 0.001 (analysis of variance). This had no effect...

  13. Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis

    DEFF Research Database (Denmark)

    Johnsen, C R; Abrahamsen, L; Stahl Skov, P;

    1991-01-01

    The aim was to compare IgE and IgG4 RAST-inhibition assay (RI), monoclonal antibody ELISA (Mab-ELISA), counter current immuno electrophoresis (CCIE) and histamine release from basophil leukocytes (HR) for allergen quantification with special reference to aeroallergen detection. As components...... and Derm. pter. (10-10(2) SQ-U/ml), and 10(2)-10(3) SQ-U/ML for dog. Because of cross-reactivity, a minor degree of interference was observed in the IgE-RI and the HR test for the highest concentration of cat and dog allergens....

  14. Allergic rhinitis is a local disease: the role of local IgE production, basophils and mast cells

    NARCIS (Netherlands)

    A. Kleinjan (Alex)

    2002-01-01

    textabstractThe introduction to this thesis summarizes the literature which indicates that there is a discrepancy between sensitisation and allergic disease. Two aspects which might play a role in this discrepancy are the differences between production and funtion of local versus systemic lgE and th

  15. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  16. Dendritic Cell-Mediated T Cell Proliferation -A Functional Bioindicator of Inflammatory Source-Specific Particulate Matter

    Science.gov (United States)

    Previously we found that dendritic cells (DC) were sensitive functional bioindicators of ambient PM (APM) exposure mediating Th2-allergic inflammation in the draining lymph nodes. Here, the ability of bone-marrow-derived DC (DC) and putative BM-derived basophils (Ba) to present a...

  17. Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

    Science.gov (United States)

    Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

    2017-01-01

    B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10−9) with opposing effects between CLL (P = 1.97 × 10−8) and HL (P = 3.31 × 10−3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10−12) was associated with increased CLL and HL risk (P = 4.68 × 10−12), and reduced MM risk (P = 1.12 × 10−2), and Gly70 in HLA-DQB1 (P = 3.15 × 10−10) showed opposing effects between CLL (P = 3.52 × 10−3) and HL (P = 3.41 × 10−9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs. PMID:28112199

  18. Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

    Science.gov (United States)

    Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio Da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

    2017-01-01

    B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10‑9) with opposing effects between CLL (P = 1.97 × 10‑8) and HL (P = 3.31 × 10‑3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10‑12) was associated with increased CLL and HL risk (P = 4.68 × 10‑12), and reduced MM risk (P = 1.12 × 10‑2), and Gly70 in HLA-DQB1 (P = 3.15 × 10‑10) showed opposing effects between CLL (P = 3.52 × 10‑3) and HL (P = 3.41 × 10‑9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.

  19. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

    DEFF Research Database (Denmark)

    Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

    2016-01-01

    BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less to...

  20. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    DEFF Research Database (Denmark)

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W

    2012-01-01

    with historical controls, we performed a retrospective national population-based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15-91 years......Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared......). The 5-year projected event-free survival (pEFS(5y) ) and overall survival (pOS(5y) ) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4-33·6] and 34·1% (95% CI 28·7-40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively...

  1. Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

    Directory of Open Access Journals (Sweden)

    K. Brandt

    2010-10-01

    Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

  2. Chronic Myeloid Leukaemia Presenting as Bilateral Retinal Haemorrhages with Multiple Retinal Infiltrates.

    Science.gov (United States)

    Rane, Priyanka Ramkrishna; Barot, Rakesh K; Gohel, Devadatta Jayantilal; Bhagat, Nupur

    2016-05-01

    Chronic Myeloid Leukaemia (CML) causes retinopathy manifesting as venous dilation and tortuosity, perivascular sheathing, retinal haemorrhages, microaneurysms, cotton-wool spots and optic nerve infiltration. Retina is the most commonly involved intraocular structure in CML. However, retinal involvement is a rare form of presentation of CML and few cases have been reported. We report a case of CML presenting as unilateral sudden visual loss. Fundus showed multiple white centered retinal haemorrhages in both eyes with unilateral macular oedema. Blood work-up showed raised WBC count, high platelet count and low Haemoglobin. Cytological analysis of bone marrow biopsy confirmed Philadelphia chromosome. After a course of Imatinib, visual acuity improved and haemorrhages resolved with normalization of macular thickness. In our case, patient presented early, leading to early detection producing better visual prognosis. This highlights the importance of detailed hematological work up in patients with retinal involvement to rule out leukaemic retinopathy.

  3. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

  4. The development of integrated haematopathology laboratories: a new approach to the diagnosis of leukaemia and lymphoma.

    Science.gov (United States)

    Richards, S J; Jack, A S

    2003-12-01

    The diagnosis and monitoring of leukaemia and lymphoma requires the effective integration of a wide range of diagnostic techniques and expertise. The need to develop this type of service that crosses traditional boundaries of laboratory specialities is being recommended in national guidance. The Haematological Malignancy Diagnostic Service based within the Leeds Teaching Hospitals NHS Trust was established in 1993 to provide specialist laboratory services for the diagnosis of haematological malignancy for Yorkshire and Humberside in the UK. The department uses a wide range of methodologies including morphology, immunocytochemistry, flow cytometry and molecular genetics [fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR)] in a systematic and co-ordinated way. We describe how the department was established, its current working practices and highlight the advantages of an integrated laboratory for diagnosis of tumours of the haematopoietic system.

  5. Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia.

    Science.gov (United States)

    Curtis, Claire E; Grand, Francis H; Musto, Pellegrino; Clark, Andrew; Murphy, John; Perla, Gianni; Minervini, Maria M; Stewart, Janet; Reiter, Andreas; Cross, Nicholas C P

    2007-07-01

    We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2), respectively, in association with BCR-ABL and FIP1L1-PDGFRA negative chronic eosinophilic leukaemia. Molecular analysis revealed a novel STRN-PDGFRA fusion for the t(2;4) and ETV6-PDGFRA for the t(4;12). The fusions were confirmed by specific amplification of the genomic breakpoints, reverse transcription polymerase chain reaction and fluorescence in situ hybridisation. Both patients were treated with imatinib and, following a rapid haematological response, achieved cytogenetic remission and a major molecular response. In conclusion, PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of these fusions is important as they are particularly sensitive to imatinib.

  6. Detection of Bovine Leukaemia Virus Antibodies and Proviral DNA in Colostrum Replacers.

    Science.gov (United States)

    Choudhury, B; Finnegan, C; Phillips, A; Horigan, M; Pollard, T; Steinbach, F

    2015-10-01

    Great Britain has been bovine leukaemia virus (BLV) disease free since 1999. We recently reported three separate incidents of BLV seropositivity on farms with home-reared cattle due to the use of colostrum replacer rather than infection with BLV (Emerg. Infect. Dis., 19, 2013, 1027). These cases were all linked via the use of the same brand of colostrum replacer. Here, we investigate further by examining multiple brands of colostrum replacer for proviral DNA and BLV antibodies. BLV antibodies were detected in 7 of the colostrum replacers tested, with PCR concurring in two cases. Thus, the use of these BLV antibody-positive colostrum replacers may also lead to false-positive serological diagnostics.

  7. Amphotropic murine leukaemia virus envelope protein is associated with cholesterol-rich microdomains

    Directory of Open Access Journals (Sweden)

    Pedersen Lene

    2005-04-01

    Full Text Available Abstract Background Cholesterol-rich microdomains like lipid rafts were recently identified as regions within the plasma membrane, which play an important role in the assembly and budding of different viruses, e.g., measles virus and human immunodeficiency virus. For these viruses association of newly synthesized viral proteins with lipid rafts has been shown. Results Here we provide evidence for the association of the envelope protein (Env of the 4070A isolate of amphotropic murine leukaemia virus (A-MLV with lipid rafts. Using density gradient centrifugation and immunocytochemical analyses, we show that Env co-localizes with cholesterol, ganglioside GM1 and caveolin-1 in these specific regions of the plasma membrane. Conclusions These results show that a large amount of A-MLV Env is associated with lipid rafts and suggest that cholesterol-rich microdomains are used as portals for the exit of A-MLV.

  8. Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hoy, Sheridan M

    2015-02-01

    Obinutuzumab (Gazyva(®); Gazyvaro(®)) is an intravenously administered, glycoengineered, humanized, type II, anti-CD20 monoclonal antibody of the IgG1 subclass. It is available in the EU and the USA as combination therapy with oral chlorambucil in adults with previously untreated chronic lymphocytic leukaemia (CLL). In a multinational phase III study in this patient population, obinutuzumab plus chlorambucil significantly prolonged progression-free survival compared with oral chlorambucil alone and intravenous rituximab plus oral chlorambucil. Significant advantages with obinutuzumab plus chlorambucil over chlorambucil alone and rituximab plus chlorambucil were also observed in event-free survival, the time to a new anti-leukaemia treatment and overall response. The overall survival benefit with obinutuzumab plus chlorambucil is as yet unclear, although the most recent analysis suggests a benefit over chlorambucil alone. In the phase III study, obinutuzumab plus chlorambucil had a manageable tolerability profile in accordance with what would be expected for an anti-CD20 antibody. Neutropenia and infusion-related reactions were the most frequently reported grade 3 or higher treatment-emergent adverse events. In the majority of patients, infusion-related reactions were mild to moderate in severity and occurred predominantly during the first infusion and were managed by slowing or temporarily halting the infusion. Thus, current evidence suggests that obinutuzumab plus chlorambucil is a welcome addition to the treatment options currently available for adults with previously untreated CLL and is recommended by the National Comprehensive Cancer Network guidelines as the preferred first option for some, including those with comorbidities.

  9. Population preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility study

    Directory of Open Access Journals (Sweden)

    Meiklejohn David

    2010-05-01

    Full Text Available Abstract Background Given that treatments for chronic lymphocytic leukaemia (CLL are palliative rather than curative, evaluating the patient-perceived impacts of therapy is critical. To date, no utility (preference studies from the general public or patient perspective have been conducted in CLL. The objective of this study was to measure preferences for health states associated with CLL treatment. Methods This was a cross-sectional study of 89 members of the general population in the UK (England and Scotland. Using standard gamble, each participant valued four health states describing response status, six describing treatment-related toxicities based on Common Toxicity Criteria, and two describing line of treatment. The health states incorporated standardized descriptions of treatment response (symptoms have "improved," "stabilized," or "gotten worse", swollen glands, impact on daily activities, fatigue, appetite, and night sweats. Utility estimates ranged from 0.0, reflecting dead, to 1.0, reflecting full health. Results Complete response (CR was the most preferred health state (mean utility, 0.91, followed by partial response (PR, 0.84; no change (NC, 0.78; and progressive disease (PD, 0.68. Among the toxicity states, grade I/II nausea and nausea/vomiting had the smallest utility decrements (both were -0.05, and grade III/IV pneumonia had the greatest decrement (-0.20. The utility decrements obtained for toxicity states can be subtracted from utilities for CR, PR, NC, and PD, as appropriate. The utilities for second- and third-line treatments, which are attempted when symptoms worsen, were 0.71 and 0.65, respectively. No significant differences in utilities were observed by age, sex, or knowledge/experience with leukaemia. Conclusions This study reports UK population utilities for a universal set of CLL health states that incorporate intended treatment response and unintended toxicities. These utilities can be applied in future cost

  10. Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R.H.; Major, I.R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1983-01-01

    The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

  11. Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

    Science.gov (United States)

    Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R; del Carmen Rodriguez-Zepeda, M; Rangel-López, A; Dorantes-Acosta, E M; Núñez-Villegas, N; Velazquez-Aviña, M M; Torres-Nava, J R; Reyes-Zepeda, N C; Cárdenas-Cardos, R; Flores-Villegas, L V; Martinez-Avalos, A; Salamanca-Gómez, F; Gorodezky, C; Arellano-Galindo, J; Mejía-Aranguré, J M

    2013-01-01

    Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. Results: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47–11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20–0.91). Conclusion: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS. PMID:23695017

  12. A Fatal Case of Acute Myeloid Leukaemia-Methotrexate Related or Primary Autoimmune Disease Related: A Rare Case Report.

    Science.gov (United States)

    Agarwal, Saurabh; Kaeley, Nidhi; Gupta, Priyanka; Gupta, Vibha; Bhatia, Rohan

    2016-03-01

    Methotrexate is being used for many years in the treatment of chronic medical disorders e.g. rheumatoid arthritis since 1951. It has been associated with various systemic toxicities and complications including bone marrow suppression and lymphomas. The development of leukaemia in a patient of chronic rheumatoid arthritis is either related with the primary disease or due to the drugs which are used in the treatment like cyclophosphamide. In our present case, a 70-year-old female who was a known case of Rheumatoid Arthritis (RA) and was on methotrexate once a week orally for the past 20 years presented with complaints of loss of appetite, loss of weight and anaemia since 2 months. After thorough examination and investigation, she was diagnosed with acute myeloid leukaemia (AML-M4) with bilateral chest consolidation.

  13. Treatment of adult lymphoblastic leukaemia using cyclical chemotherapy with three combinations of four drugs (COAP, POMP, TRAP schedule).

    Science.gov (United States)

    Proctor, S J; Finney, R; Walker, W; Thompson, R B

    1981-01-01

    Seventeen adult patients with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a schedule of chemotherapy in which 3 combinations, each of 4 drugs, were administered in a predetermined cyclical rotation in combination with cranial irradiation and intrathecal injections of methotrexate. Of the 17 patients, 16 completed induction therapy and 15 (94%) entered remission. The only patient with T-ALL died before receiving any therapy. The median survival for all patients (17) was 22 months. Meningeal leukaemia did not occur during the haematological remission phase although 3 patients developed this complication following relapse. The authors conclude that the addition of cyclophosphamide and cytosine arabinoside to vincristine/prednisone provides excellent remission induction but the aggressive maintenance schedule employed has not led to significant long-term survival.

  14. Fish oil supplementation is beneficial on caloric intake, appetite and mid upper arm muscle circumference in children with leukaemia.

    Science.gov (United States)

    Abu Zaid, Zalina; Shahar, Suzana; Jamal, A Rahman A; Mohd Yusof, Noor Aini

    2012-01-01

    A randomised trial was carried out to determine the effect of supplementation of fish oil among 51 children with leukaemia aged 4 to 12 years on appetite level, caloric intake, body weight and lean body mass. They were randomly allocated into the trial group (TG) and the control group (CG). At baseline, 30.8% of TG subjects and 44.0% of CG subjects were malnourished and 7.7% of subject from TG and 28.0% from CG were classified as stunted. The majority of subjects from TG and CG were in the mild malnutrition category for mid upper arm muscle circumference (MUAMC)-for-age. The TG group showed significant increment in MUAMC (0.13 cm vs -0.09 cm) compared with CG at 8 weeks (pappetite level (0.12±0.33) (pappetite level, caloric intake and MUAMC among children with leukaemia.

  15. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

    Science.gov (United States)

    Rees, J K; Gray, R G; Wheatley, K

    1996-07-01

    Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

  16. Heterogeneity in the therapeutic approach to relapsed elderly patients with acute myeloid leukaemia: a survey from the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Acute Leukaemia Working Party.

    Science.gov (United States)

    Ferrara, Felicetto; Fazi, Paola; Venditti, Adriano; Pagano, Livio; Amadori, Sergio; Mandelli, Franco

    2008-06-01

    The percentage of long-term survivors in acute myeloid leukaemia (AML) in the elderly does not exceed 10-15% of patients enrolled into clinical trials because of lower complete remission (CR) rates and higher incidence of relapse. However, few data are available as the treatment of elderly patients with relapsed disease is concerned. The aim of this study was of collecting data on criteria adopted for the treatment of these patients. A questionnaire was e-mailed to 32 haematologic institutions involved in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group. Questions to be addressed regarded: (1) per cent of relapsed elderly patients treated with aggressive salvage chemotherapy; (2) the selection criteria adopted for inclusion into intensive reinduction; (3) the specific treatment adopted; (4) the treatment given to patients not eligible for intensive salvage. Per cent of patients enrolled into aggressive salvage regimens varied from 10 to 80% (median 50%). The most frequent factor influencing the therapeutic choice was performance status (97%). Additional factors were age >70 years (44%) and duration of first CR (53%). Fludarabine including regimens were most frequently used as aggressive salvage therapy (59%), while gemtuzumab ozogamicin was adopted in various combinations at 11 out of 32 institutions (34%). For patients not eligible to aggressive therapy, the most frequent approach included hydroxyurea (59%). Low dose ARA-C (LDARA-C) was adopted at five centres: as single agent (n = 1), with 6-thioguanine (n = 1), with vitamin D3 and all-trans retinoic acid (ATRA) (n = 2), or with ATRA alone (n = 1). The FLT3 inhibitor CEP-701 was used at one centre. We conclude that the treatment of AML in elderly relapsed patients is extremely heterogeneous. A marked selection is operated as to inclusion into aggressive salvage regimens and only a small minority of patients are offered experimental approaches.

  17. Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

    Science.gov (United States)

    Beckman, I G; Bradley, J; Brooks, D A; Kupa, A; McNamara, P J; Thomas, M E; Zola, H

    1980-06-01

    A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen.

  18. Novel X-linked inhibitor of apoptosis inhibiting compound as sensitizer for TRAIL-mediated apoptosis in chronic lymphocytic leukaemia with poor prognosis.

    Science.gov (United States)

    Frenzel, Lukas P; Patz, Michaela; Pallasch, Christian P; Brinker, Reinhild; Claasen, Julia; Schulz, Alexandra; Hallek, Michael; Kashkar, Hamid; Wendtner, Clemens-Martin

    2011-01-01

    Given that aggressive DNA damaging chemotherapy shows suboptimal efficacy in chronic lymphocytic leukaemia (CLL), alternative therapeutic approaches are needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce tumour-specific apoptosis. However, apoptosis might be inhibited by elevated levels of X-linked inhibitor of apoptosis (XIAP). Use of XIAP-inhibiting compounds might sensitize primary CLL cells towards TRAIL-mediated apoptosis. A novel small molecule, compound A (CA), an inhibitor of XIAP, was used in combination with TRAIL to induce apoptosis in primary CLL cells (n = 48). XIAP was significantly more highly expressed in primary CLL cells (n = 28) compared to healthy B cells (n = 16) (P = 0·02). Our data obtained by specific knock-down of XIAP by siRNA identified XIAP as the key factor conferring resistance to TRAIL in CLL. Combined treatment with CA/TRAIL significantly increased apoptosis compared to untreated (P = 8·5 × 10⁻¹⁰), solely CA (P = 4·1 × 10⁻¹²) or TRAIL treated (P = 4·8 × 10⁻¹⁰) CLL cells. CA rendered 40 of 48 (83·3%) primary CLL samples susceptible to TRAIL-mediated apoptosis. In particular, cells derived from patients with poor prognosis CLL (ZAP-70(+) , IGHV unmutated, 17p-) were highly responsive to this drug combination. Our highly-effective XIAP inhibitor CA, in concert with TRAIL, shows potential for the treatment of CLL cases with poor prognosis and therefore warrants further clinical investigation.

  19. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013.

    Science.gov (United States)

    Yeoh, Allen E J; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2013-11-01

    Survival for adults and children with acute lymphoblastic leukaemia has risen substantially in recent years because use of improved risk-directed treatments and supportive care has widened. In nearly all developed countries, multidisciplinary panels of leukaemia experts have formulated clinical practice guidelines in which standard treatment approaches are recommended on the basis of current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, huge disparities in economy and infrastructure exist between countries, and even among different regions in some large countries. At a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand, a panel of experts summarised recommendations for management of adult and paediatric acute lymphoblastic leukaemia. Strategies were developed for Asian countries on the basis of available financial, skill, and logistical resources and were stratified in a four-tier system according to the resources available in a particular country or region (basic, limited, enhanced, and maximum).

  20. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013

    Science.gov (United States)

    Yeoh, Allen EJ; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2014-01-01

    The survival rates for both adult and children with acute lymphoblastic leukaemia have improved substantially in recent years with wider use of improved risk-directed therapy and supportive care. In nearly all developed countries, clinical practice guidelines have been formulated by multidisciplinary panels of leukaemia experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, there are huge disparities in economy and infrastructure among the countries, and even among different regions in some large countries. This review summarizes the recommendations developed for Asian countries by a panel of adult and paediatric leukaemia therapists, based on the availability of financial, skill and logistical resources, at a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. The management strategies described here are stratified by a four-tier system (basic, limited, enhanced and maximum) based on the resources available to a particular country or region. PMID:24176570

  1. The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy.

    Science.gov (United States)

    Malihi, Z; Kandiah, M; Chan, Y M; Esfandbod, M; Vakili, M; Hosseinzadeh, M; Zarif Yeganeh, M

    2015-07-01

    This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24-h recall and a 136-item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy-related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.

  2. Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I.

    Science.gov (United States)

    van Ree, R; Aalberse, R C

    1995-03-01

    The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.

  3. [Renal infiltrate by a plasmocytoïd chronic B lymphocytic leukaemia and renal failure: a rare occurrence in nephropathology. A case report and review of the literature].

    Science.gov (United States)

    Aymard, Bernadette; Beghoura, Rachid; Molina, Thierry Jo

    2011-11-01

    We report the case of a 55-year-old male with renal failure as the initial manifestation of interstitial and focal infiltration of the kidneys by a small B-cell lymphoma. Since three years, this patient had a history of CLL with plasmocytic differentiation and was left untreated owing to stade A Binet classification. After chemotherapy, the lymphocytosis and the adenopathies disappear and the renal function improve. Infiltration of the kidneys by non-Hodgkin small B-cell lymphoma, including chronic lymphocytic leukaemia (CLL), is usually asymptomatic, fortuitously discovered at the time of an X-ray examination or at autopsy. Association with renal failure is extremely rare. We review the reported cases of renal failure associated with lymphomatous infiltration (13 cases of CLL and five cases of lymphoplasmocytic lymphoma kappa or lambda IgM), with the following conclusions: in most cases, renal insufficiency appears in a few months and significantly disappears after chemotherapy; the renal infiltrate is usually focal in lymphoplasmocytic lymphoma and rather massive and diffuse in CLL; the neoplastic feature of a small B-cell lymphoïd infiltrate may be difficult to determine: a poorly limited, monomorphous, CD20+ CD5+ lymphoid infiltrate is lymphomatous. In case of plasmocytic differentiation, it must be looked for kappa or lambda monotypy; the type of the lymphomatous infiltrate according to the WHO 2008 classification may be difficult to determine in a small sampling of renal tissue: the renal infiltrate must be compared, if possible, with a lymph node infiltrate. Owing to its bad prognosis, mantle cell lymphoma must be distinguished from other small B-cell lymphoma like CLL/small lymphocytic lymphoma, marginal zone lymphoma and lymphoplasmocytic lymphoma.

  4. Mast Cell Growth Factor Enhances Multilineage Hematopoietic Recovery in Vivo Following Radiation-Induced Aplasia

    Science.gov (United States)

    1994-01-01

    lymphocyte, monocyte, tributing to morbidity and mortality associated with hemato- eosinophil , and basophil numbers, as well as an increase in...factor (ligand for c-kit) administered in murine mast cell growth factor (c-kit figand) on colony vivo to mice either alone or in combination with granu

  5. Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-de pendent upregulation

    Institute of Scientific and Technical Information of China (English)

    Florian HENNERSDORF; Stefan FLORIAN; Andreas JAKOB; Katharina BAUMG(A)RTNER; Karoline SONNECK; Alfred NORDHEIM; Tilo BIEDERMANN; Peter VALENT; Hans-J(o)rg B(U)HRING

    2005-01-01

    Using two-colour flow cytometry >200 antibodies submitted to the 8th International Workshop of Human Leukocyte Differentiation Antigens (HLDA8) have been analyzed for their reactivity with resting and activated CD203c+ basophils.Four antibodies either non-reactive or weakly reactive with resting basophils exhibited an increased reactivity with basophils activated by anti-IgE-mediated cross-linking of the high affinity IgE receptor (FcεRI). These include antibodies against CD164 (WS-80160, clone N6B6 and WS-80162, clone 67D2), as well as two reagents with previously unknown specificities that were identified as CD13 (WS-80274, clone A8) and CD107a (WS-80280, clone E63-880).The activation patterns followed either the "CD203c-like" or "CD63-like" activation profile. The CD203c profile is characterized by a rapid and significant upregulation (of CD13, CD164, and CD203c), reaching maximum levels after 5-15 min of stimulation. The Phosphoinositide-3-kinase (PI3K)-specific inhibitor Wortmannin inhibited the upregulation of these markers whereas 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced a rapid and FcεRI-independent upregulation within 1-2 min. In the CD63 profile, maximum upregulation (of CD63 and CD107a) was detected only after 20-40 min,and upregulation by TPA reached maximum levels after 60 min. In summary, our data identify CD13, CD107a, and CD164 as novel basophil-activation antigens. Based on time kinetics of upregulation, we hypothesize that molecules of the "CD203c group" and the "CD63 group" are linked to two different mechanisms of basophil activation.

  6. An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases.

    Science.gov (United States)

    Worrillow, L; Baskaran, P; Care, M A; Varghese, A; Munir, T; Evans, P A; O'Connor, S J; Rawstron, A; Hazelwood, L; Tooze, R M; Hillmen, P; Newton, D J

    2016-10-06

    Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases.

  7. Molecular expression of l-asparaginase gene from Nocardiopsis alba NIOT-VKMA08 in Escherichia coli: A prospective recombinant enzyme for leukaemia chemotherapy.

    Science.gov (United States)

    Meena, Balakrishnan; Anburajan, Lawrance; Vinithkumar, Nambali Valsalan; Shridhar, Divya; Raghavan, Rangamaran Vijaya; Dharani, Gopal; Kirubagaran, Ramalingam

    2016-09-30

    l-Asparaginase is an antineoplastic agent that selectively reduces the level of l-asparagine in blood and diminishes the proliferation of cancerous cells. Studies were carried out on the cloning and heterologous expression of l-asparaginase biosynthesis gene (ansA) from Nocardiopsis alba NIOT-VKMA08 to achieve the stable inducible system that overproduces the glutaminase-free recombinant l-asparaginase. Overexpression of recombinant l-asparaginase was achieved with an optimized final concentration of 1.5mM of isopropyl-β-d-thiogalactoside (IPTG) and the enzyme was expressed as a soluble protein. The recombinant enzyme was purified using nickel-nitrilotriacetic acid (Ni-NTA) chromatography and the purified enzyme disclosed an elevated level of asparaginase activity (158.1IU/mL). Optimum pH and temperature of the purified l-asparaginase for the hydrolysis of l-asparagine were 8.0 and 37°C and it was very specific for its natural substrate, l-asparagine. Detailed studies were carried out on the kinetics of enzyme reaction, catalytic activity, temperature and ionic strength and the thermostability of the l-asparaginase enzyme. The functional characterisation of the recombinant l-asparaginase was studied through Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), in silico sequence analysis and protein structural modelling. Glutaminase activity was not detected in the recombinant l-asparaginase, which could reduce the probable side effects during leukaemia therapy.

  8. Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV and the Koala Retrovirus (KoRV

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-12-01

    Full Text Available Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1 is a well-known example. The gibbon ape leukaemia virus (GaLV and koala retrovirus (KoRV, two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs during xenotransplantation using pig cells, tissues or organs.

  9. Massive myeloid sarcoma affecting the central nervous system, mediastinum, retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia: a case report

    Science.gov (United States)

    Best-Aguilera, C R; Vazquez-Del Mercado, M; Muñoz-Valle, J F; Herrera-Zarate, L; Navarro-Hernandez, R E; Martin-Marquez, B T; Oregon-Romero, E; Ruiz-Quezada, S; Bonilla, G M; Lomeli-Guerrero, A

    2005-01-01

    Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When associated with acute myelogenous leukaemia (AML), these tumours usually affect no more than two different extramedullary regions. This report describes a myeloid sarcoma associated with AML with tumour formation at five anatomical sites. The patient was a 37 year old man admitted in September 1999 with a two month history of weight loss, symptoms of anaemia, rectal bleeding, and left facial nerve palsy. The anatomical sites affected were: the rectum, the right lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous system. A bone marrow smear was compatible with AML M2. Flow cytometry showed that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The presence of multiple solid tumours in AML is a rare event. Enhanced expression of cell adhesion molecules may be the reason why some patients develop myeloid sarcomas. PMID:15735171

  10. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

    Science.gov (United States)

    Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

    2017-01-01

    Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities

  11. Hyperthyroidism after Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukaemia: A Case Report and Literature Review%慢性髓性白血病患者非血缘供者骨髓移植术后并发甲状腺功能亢进1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    臧学峰; 李渤涛; 庞一琳; 刘婷婷; 楼晓; 李倩; 江岷; 王雷; 陈虎

    2013-01-01

    目的:分析骨髓移植后引起甲状腺功能亢进的病因、临床特点、治疗及预后.方法:报道l例慢性髓性白血病患者非血缘供者骨髓移植术后并发甲状腺功能亢进随访9年的结果,并复习相关文献.结果:患者男性,21岁,确诊慢性髓性白血病后行非血缘供者骨髓移植,术后+44天,出现持续低热,抗细菌、抗病毒及抗真菌治疗均无效,排除疾病复发,查甲状腺功能提示患者从亚临床甲状腺功能亢进进展为甲状腺功能亢进,给予口服甲巯咪唑治疗2周,患者体温降至正常,血T4、fT4恢复正常,随访9年,慢性髓性白血病无复发,甲状腺功能持续正常.检索文献发现类似报道5例,对其进行归纳分析.结论:骨髓移植术后早期并发甲状腺功能亢进,可能与放化疗预处理及免疫损伤引起的破坏性甲状腺炎相关,有其独特的临床表现,极易被忽视,治疗方面可以尝试应用糖皮质激素及抗甲状腺药物.对于非血缘供者骨髓移植后不明原因发热者,应考虑到甲亢可能.%Objective: To analyze the pathogenesis of hyperthyroidism after hematopoietic stem cell transplantation (HSCT), and study the clinical characteristics, therapy and prognosis of early onset hyperthyroidism. Methods: One case of chronic myeloid leukemia (CML) after matched unrelated bone marrow transplantation (MUD-BMT) complicated with hyperthyroidism was reported, and its related literature was reviewed. Results: A 21-year-old male with a definitive diagnosis of CML came for a treatment of MUD-BMT. 44 days after transplantation, the patient presented with sustained low fever which was not response to antibiotic, antiviral or antifungal therapy. Excluded from disease recurrence, he was found to have a progress from subclinical hyperthyroidism to clinical hyperthyroidism. After two weeks therapy of methimazole, his temperature become normal, as well as T4, fT4. With a follow up of 9 years, he had no recurrence of

  12. CLONAL CHRONIC LYMPHOCYTIC LEUKEMIA-LIKE B-LYMPHOCYTES IN THE BLOOD OF PATIENTS WITH CUTANEOUS T-CELL DISORDERS

    NARCIS (Netherlands)

    DAENEN, S; VADER, PCV; BLOM, N; PIETENS, J; HOLLEMA, H; SMIT, JW

    1993-01-01

    A population of B cells with characteristics of chronic lymphocytic leukaemia was found in the peripheral blood of four patients who presented with cutaneous infiltration of atypical CD4+ T cells with cerebriform nuclei. The B cells had a low density of immunoglobulin on their surface membrane, expr

  13. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Canninga-van Dijk, MR; Sanders, CJ; Verdonck, LF; Fijnheer, R; van den Tweel, JG

    2003-01-01

    Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency s

  14. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

    Science.gov (United States)

    González, A; Cortina, L; González, P; González, C; García, T; de Svarch, E G

    2004-05-01

    Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

  15. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina.

    Science.gov (United States)

    Monti, G E; Frankena, K; De Jong, M C M

    2007-02-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 lactating cows. Time-interval parameters were analysed using a parametric survival model with shared frailty, time until infection was analysed using a Bayesian interval-censoring survival model and the infection transmission parameter (beta) was estimated by a generalized linear model. The reproduction ratio (R0) was calculated. In total, 1000 cows tested positive and 494 tested negative. The predicted median age at infection was 4.6 years for seroconverted cows. For infected herds, the proportion of positive calves was as high as for infected cows and showed a large proportion of infected breeding heifers. Peaks in the overall average incidence per season-year were observed during autumn and spring. Results reveal that the period around parturition is a high-risk period. Moreover, heavily infected herds seem to have an increased proportion of young stock infected. The overall beta was estimated as 2.9/year (95% CI 1.9-3.7) and combined with a relatively long infectious period it resulted in a high reproductive ratio (R0=8.9). Therefore, a high effectiveness of control measures needs to be achieved to eradicate the disease.

  16. Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Wang, Jingting; Yao, Nengliang; Wang, Yuanyuan; Zhou, Fen; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-04-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies.

  17. Symptom experience and management among people with acute myeloid leukaemia in Thailand.

    Science.gov (United States)

    Temtap, Suthisa; Nilmanat, Kittikorn

    2011-08-01

    In Thailand, haematological malignancy is one of the most common types of cancer. This cross-sectional study, conducted in Southern Thailand, aimed to describe the symptom experiences of and symptom management strategies among patients with acute myeloid leukaemia (AML). Sixty hospitalized patients with AML were recruited. The Symptom Experience Scale and two open-ended questions regarding symptom-management strategies were used to collect data via face-to-face interviews 2 weeks after the induction phase of the AML protocol. The data was analysed using descriptive statistics and content analysis. High fever, weakness, nausea, and anorexia were the four most prevalent symptoms reported. Other prevalent symptoms included weight loss, bleeding, nausea and vomiting, dysphagia, and a cluster of psycho-emotional symptoms: worrying, fear, feeling discouraged, and feeling bored. Patients used various approaches and strategies to alleviate their symptoms, which could be categorized into five groups: preventive, direct, distraction, complementary, and restorative approaches. This study has provided important information for the development of symptom-management nursing programmes for patients with AML, particularly in Thailand.

  18. Impact of NOD2 polymorphisms on infectious complications following chemotherapy in patients with acute myeloid leukaemia.

    Science.gov (United States)

    Yomade, Olaposi; Spies-Weisshart, Bärbel; Glaser, Anita; Schnetzke, Ulf; Hochhaus, Andreas; Scholl, Sebastian

    2013-08-01

    We sought to investigate the relationship between polymorphisms of the NOD2 gene and infectious complications following intensive induction chemotherapy in patients with acute myeloid leukaemia (AML). We hypothesised that single nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher rate of infections during the phase of severe neutropenia. In 131 AML patients receiving induction therapy, the presence of the three most frequent polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP analyses by means of genomic PCR incorporating fluorescence-labelled probes with characteristic melting curves were performed using the LightCycler platform. Our data suggest a significantly lower probability of mucositis or enteritis in AML patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore, bloodstream cultures of AML patients carrying either a missense or a frameshift mutation of NOD2 were significantly more frequently tested positive concerning Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact on such important infectious complications as systemic inflammatory response syndrome or sepsis, the rate of central venous catheter infections or the incidence of pneumonia including fungal infections. Our data represent one of the first reports investigating the impact of polymorphisms of the innate immune system on infectious complications in patients with neutropenia following chemotherapy. A correlation between NOD2 polymorphisms and infectious events in AML patients is demonstrated.

  19. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    Science.gov (United States)

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  20. Extracellular-like matrices and leukaemia inhibitory factor for in vitro culture of human primordial follicles.

    Science.gov (United States)

    Younis, Assiel J; Lerer-Serfaty, Galit; Stav, Dana; Sabbah, Bethsabee; Shochat, Tzippy; Kessler-Icekson, Gania; Zahalka, Muayad A; Shachar-Goldenberg, Michal; Ben-Haroush, Avi; Fisch, Benjamin; Abir, Ronit

    2017-02-01

    The possibility of maturing human primordial follicles in vitro would assist fertility restoration without the danger of reseeding malignancies. Leukaemia inhibitory factor (LIF) and certain culture matrices may promote human follicular growth. The present study compared human primordial follicular growth on novel culture matrices, namely human recombinant vitronectin (hrVit), small intestine submucosa (SIS), alginate scaffolds and human recombinant virgin collagen bioengineered in tobacco plant lines (CollPlant). The frozen-thawed ovarian samples that were used had been obtained from girls or young women undergoing fertility preservation. In the first part of the study, 20 samples were cultured for 6 days on hrVit or SIS with basic culture medium alone or supplemented with one of two concentrations of LIF (10ngmL-1 and 100ngmL-1), with and without LIF-neutralising antibody. In the second part of the study, 15 samples were cultured for 6 days on alginate scaffolds or CollPlant matrices with basic culture medium. Follicular development was assessed by follicular counts and classification, Ki67 immunohistochemistry and 17β-oestradiol and anti-Müllerian hormone measurements in spent media samples. Primordial follicular growth was not enhanced by LIF. Despite some significant differences among the four matrices, none appeared to have a clear advantage, apart from significantly more Ki67-stained follicles on alginate and CollPlant matrices. Further studies of other culture matrices and medium supplements are needed to obtain an optimal system.