Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

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Lee Ratner

Full Text Available Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold, and virus replication occurred, coincident with development of disease progression.EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.

Human T-cell leukemia virus type 1 Tax requires direct access to DNA for recruitment of CREB binding protein to the viral promoter.

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Lenzmeier, B A; Giebler, H A; Nyborg, J K

1998-02-01

Efficient human T-cell leukemia virus type 1 (HTLV-1) replication and viral gene expression are dependent upon the virally encoded oncoprotein Tax. To activate HTLV-1 transcription, Tax interacts with the cellular DNA binding protein cyclic AMP-responsive element binding protein (CREB) and recruits the coactivator CREB binding protein (CBP), forming a nucleoprotein complex on the three viral cyclic AMP-responsive elements (CREs) in the HTLV-1 promoter. Short stretches of dG-dC-rich (GC-rich) DNA, immediately flanking each of the viral CREs, are essential for Tax recruitment of CBP in vitro and Tax transactivation in vivo. Although the importance of the viral CRE-flanking sequences is well established, several studies have failed to identify an interaction between Tax and the DNA. The mechanistic role of the viral CRE-flanking sequences has therefore remained enigmatic. In this study, we used high resolution methidiumpropyl-EDTA iron(II) footprinting to show that Tax extended the CREB footprint into the GC-rich DNA flanking sequences of the viral CRE. The Tax-CREB footprint was enhanced but not extended by the KIX domain of CBP, suggesting that the coactivator increased the stability of the nucleoprotein complex. Conversely, the footprint pattern of CREB on a cellular CRE lacking GC-rich flanking sequences did not change in the presence of Tax or Tax plus KIX. The minor-groove DNA binding drug chromomycin A3 bound to the GC-rich flanking sequences and inhibited the association of Tax and the Tax-CBP complex without affecting CREB binding. Tax specifically cross-linked to the viral CRE in the 5'-flanking sequence, and this cross-link was blocked by chromomycin A3. Together, these data support a model where Tax interacts directly with both CREB and the minor-groove viral CRE-flanking sequences to form a high-affinity binding site for the recruitment of CBP to the HTLV-1 promoter.

Inability of Kaplan radiation leukemia virus to replicate on mouse fibroblasts is conferred by its long terminal repeat

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Rassart, E.; Paquette, Y.; Jolicoeur, P.

1988-01-01

The molecularly cloned infectious Kaplan radiation leukemia virus has previously been shown to be unable to replicate on mouse fibroblasts. To map the viral sequences responsible for this, we constructed chimeric viral DNA genomes in vitro with parental cloned infectious viral DNAs from the nonfibrotropic (F-) BL/VL3 V-13 radiation leukemia virus and the fibrotropic (F+) endogenous BALB/c or Moloney murine leukemia viruses (MuLV). Infectious chimeric MuLVs, recovered after transfection of Ti-6 lymphocytes with these recombinant DNAs, were tested for capacity to replicate on mouse fibroblasts in vitro. We found that chimeric MuLVs harboring the long terminal repeat (LTR) of a fibrotropic MuLV replicated well on mouse fibroblasts. Conversely, chimeric MuLVs harboring the LTR of a nonfibrotropic MuLV were restricted on mouse fibroblasts. These results indicate that the LTR of BL/VL3 radiation leukemia virus harbors the primary determinant responsible for its inability to replicate on mouse fibroblasts in vitro. Our results also show that the primary determinant allowing F+ MuLVs (endogenous BALB/c and Moloney MuLVs) to replicate on mouse fibroblasts in vitro resides within the LTR

Pericarditis as presenting manifestation of acute nonlymphocytic leukemia in a young child.

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Chu, J Y; Demello, D; O'Connor, D M; Chen, S C; Gale, G B

1983-07-15

A case of acute nonlymphocytic leukemia presenting as pericarditis is reported in a five-year-old boy. Initially, a clinical diagnosis of viral pericarditis was made, because the child did not demonstrate hematologic or clinical manifestations of leukemia. Acute undifferentiated or lymphocytic leukemia. Acute undifferentiated or lymphocytic leukemia was diagnosed one week after admission when his peripheral blood count became abnormal. The patient did not respond to vincristine and prednisone. When cytochemical evaluation indicated acute myelomonocytic leukemia, employment of cytosine arabinoside and 6-thioguanine was instituted and the child began to improve. Currently, he is still in good remission and has no evidence of recurrence of pericarditis, 1 1/2 years after his initial presentation. In reviewing the literature, we found 17 patients who had leukemic pericardial effusion with cardiac tamponade. There are three reported cases of young children with pericardial effusion as the initial manifestation of acute lymphocytic leukemia, but no reported cases due to nonlymphocytic leukemia, as in this child.

PREVALENCE OF BOVINE HERPESVIRUS-1,PARAINFLUENZA-3,BOVINE ROTAVIRUS, BOVINE VIRAL DIARRHEA, BOVINE ADENOVIRUS-7,BOVINE LEUKEMIA VIRUS AND BLUETONGUE VIRUS ANTIBODIES IN CATTLE IN MEXICO

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SUZAN, Victor M.; ONUMA, Misao; AGUILAR, Romero E.; MURAKAMI, Yosuke

1983-01-01

Sera were collected from dairy and beef cattle in 19 different states of Mexico. These sera were tested for bovine herpesvirus-1 (BHV-1), parainfluenza-3 virus (PIV-3), bovine rotavirus (BRV), bovine leukemia virus (BLV), bovine adenovirus-7 (BAV-7), bluetongue virus (BTV) and bovine viral diarrhea virus (BVDV). Seropositive rates for each virus for dairy cattle tested were 158/277(57.0%) for BHV-1,217/286(75.0%) for PIV-3,541/1498(36.1%) for BLV, 134/144(93.1%) for BRV, 39/90(43.3%) for BTV,...

Virus inactivation studies using ion beams, electron and gamma irradiation

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Smolko, Eduardo E. [Laboratorio de Polimeros, Grupo Aplicaciones Industriales, Unidad de Aplicaciones Tecnologicas y Agropecuarias, Centro Atomico Ezeiza, Comision Nacional de Energia Atomica, Pbro. Juan Gonzalez y Aragon 15, C.P. B1802AYA Ezeiza, Buenos Aires (Argentina)]. E-mail: smolko@cae.cnea.gov.ar; Lombardo, Jorge H. [Biotech S.A., C.P. 1754 Buenos Aires (Argentina)

2005-07-01

Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle ({alpha}, d and ss) and {gamma} irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D{sub 37} dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule.

Virus inactivation studies using ion beams, electron and gamma irradiation

International Nuclear Information System (INIS)

Smolko, Eduardo E.; Lombardo, Jorge H.

2005-01-01

Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle (α, d and ss) and γ irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D 37 dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule

Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

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Reif, A.E.

1985-01-01

Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells

Human T-Cell Leukemia Virus Type I-Mediated Repression of PDZ-LIM Domain-Containing Protein 2 Involves DNA Methylation But Independent of the Viral Oncoprotein Tax

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Pengrong Yan

2009-10-01

Full Text Available Human T-cell leukemia virus type I (HTLV-I is the etiological agent of adult T-cell leukemia (ATL. Our recent studies have shown that one important mechanism of HTLV-I-Mediated tumorigenesis is through PDZ-LIM domain-containing protein 2 (PDLIM2 repression, although the involved mechanism remains unknown. Here, we further report that HTLV-I-Mediated PDLIM2 repression was a pathophysiological event and the PDLIM2 repression involved DNA methylation. Whereas DNA methyltransferases 1 and 3b but not 3a were upregulated in HTLV-I-transformed T cells, the hypomethylating agent 5-aza-2′-deoxycytidine (5-aza-dC restored PDLIM2 expression and induced death of these malignant cells. Notably, the PDLIM2 repression was independent of the viral regulatory protein Tax because neither short-term induction nor long-term stable expression of Tax could downregulate PDLIM2 expression. These studies provide important insights into PDLIM2 regulation, HTLV-I leukemogenicity, long latency, and cancer health disparities. Given the efficient antitumor activity with no obvious toxicity of 5-aza-dC, these studies also suggest potential therapeutic strategies for ATL.

Protection against Acute Lethal Viral Infections with the Native Steroid Dehydroepiandrosterone (DHEA)

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1988-01-01

of gout , hyperlipemia, and in post-coronary patients Protection Against Viral Inftiom With DHEA 311 [Regelson, 19881. In animal models [Yen, 19771 and...3333. Johnson DA, Schultz LD, Bedigian HG (1982): Immunodeficiency and reticulum cell sarcoma in mice segregating for HRS/J and SJL/J genes . Leukemia

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

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... Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

The influence of mouse vaccination with endogenous retrovirus on the development of tumor incluced by γ-irradiation or 7,12-Dimethylbenz(a)anthrocene

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Mazurenko, N.P.; Yakovleva, L.S.; Shcherbak, N.P.; Pavlovskaya, A.I.; Zueva, Yu.N.

1987-01-01

Mouse vaccination with alive endogenous N-tropic virus OA-3 inhibited and decreased the development of the Rauscher leukemia in C57B1/6 mice (B-type) and SWR mice (N-type) as well as development 7,12-dimethyl benzanthracene (DMBA) induced tumours in mouse hybrides (neither N-, nor B-types). The effect of vaccination was DMBA- or MLV-P-dose-dependent. Vaccination with the same virus did not affect the incidence of γ-irradiaton-induced leukemia in CBA mice (N-type) and C57B1/6 mice while it increased twice the incidence of radiation leukemia in DBA mice (N-type). However, the incidence of thymomas lowered in radiaton leukemia-bearing vaccinated mice of all the 3 strains, which may result from inhibition of murine thymotropic endogenous virus reproduction. The data obtained indicate the participation of murine own endogenous viruses in DMBA- or γ-irradiation induced carcinogenesis

The Role of B Cells for in Vivo T Cell Responses to a Friend Virus-Induced Leukemia

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Schultz, Kirk R.; Klarnet, Jay P.; Gieni, Randall S.; Hayglass, Kent T.; Greenberg, Philip D.

1990-08-01

B cells can function as antigen-presenting cells and accessory cells for T cell responses. This study evaluated the role of B cells in the induction of protective T cell immunity to a Friend murine leukemia virus (F-MuLV)-induced leukemia (FBL). B cell-deficient mice exhibited significantly reduced tumor-specific CD4^+ helper and CD8^+ cytotoxic T cell responses after priming with FBL or a recombinant vaccinia virus containing F-MuLV antigens. Moreover, these mice had diminished T cell responses to the vaccinia viral antigens. Tumor-primed T cells transferred into B cell-deficient mice effectively eradicated disseminated FBL. Thus, B cells appear necessary for efficient priming but not expression of tumor and viral T cell immunity.

CAR-T therapy for leukemia: progress and challenges.

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Wang, Xin; Xiao, Qing; Wang, Zhe; Feng, Wen-Li

2017-04-01

Despite the rapid development of therapeutic strategies, leukemia remains a type of difficult-to-treat hematopoietic malignancy that necessitates introduction of more effective treatment options to improve life expectancy and quality of patients. Genetic engineering in adoptively transferred T cells to express antigen-specific chimeric antigen receptors (CARs) has proved highly powerful and efficacious in inducing sustained responses in patients with refractory malignancies, as exemplified by the success of CD19-targeting CAR-T treatment in patients with relapsed acute lymphoblastic leukemia. Recent strategies, including manipulating intracellular activating domains and transducing viral vectors, have resulted in better designed and optimized CAR-T cells. This is further facilitated by the rapid identification of an accumulating number of potential leukemic antigens that may serve as therapeutic targets for CAR-T cells. This review will provide a comprehensive background and scrutinize recent important breakthrough studies on anti-leukemia CAR-T cells, with focus on recently identified antigens for CAR-T therapy design and approaches to overcome critical challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

Leukemia

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Mabuchi, Kiyohiko; Kusumi, Shizuyo

1992-01-01

Leukemia is the first malignant disease found among A-bomb survivors. Leukemia registration has greatly contributed to epidemiological and hematological studies on A-bomb radiation-related leukemia and other hematopoietic diseases, consisting of community population and the RERF Life Span Study (LSS) sample (approximately 120,000 persons containing A-bomb survivors). Using the fixed LSS cohort, the prevalence rate of leukemia reached the peak during the years 1950-1954, and thereafter, it has been gradually decreased. However, risk patterns for leukemia are still unsolved: has leukemia risk increased in recent years?; are serial changes in leukemia risk influenced by age at the time of exposure (ATE)?; is there variation between Hiroshima and Nagasaki?; and others. To solve these questions, leukemia data are now under analysis using the revised DS86. Relative risk for leukemia, especially chronic myelogenous leukemia and acute lymphocytic leukemia (ALL), is found to be linearly increased with increasing bone marrow doses. Serial patterns of both excess risk and excess relative risk have revealed that leukemia risk is high at 5-10 years after A-bombing in younger A-bomb survivors ATE. The influence of age ATE on serial changes is noticeable in ALL. Another factor involved in the prevalence of leukemia is background (spontaneously developed leukemia), which is the recent interest because young A-bomb survivors ATE reach the cancer-prone age. (N.K.)

Murine leukemia viruses: objects and organisms.

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Rein, Alan

2011-01-01

Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes-protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera.

Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections

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Enrique Fuentes-Mattei

2017-06-01

Full Text Available Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8 varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR, and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV, a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1 IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P < 0.001. The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the “gold” standard method to detect certain viral infections in clinical practice.

Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents

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Sharma, Sanjai; Murai, Fukashi; Miyanohara, Atsushi; Friedmann, Theodore

1997-01-01

Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 105 colony-forming units per ml. PMID:9380714

Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents.

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Sharma, S; Murai, F; Miyanohara, A; Friedmann, T

1997-09-30

Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 10(5) colony-forming units per ml.

Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral pathogenesis

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Benoit eBarbeau

2013-08-01

Full Text Available The production of antisense transcripts from the 3’ long terminal repeat (LTR in human T-lymphotropic retroviruses has now been clearly demonstrated. After the identification of the antisense strand-encoded HTLV-1 bZIP (HBZ factor, we reported that HBZ could interact with CREB transcription factors and consequently turn off the important activating potential of the viral Tax protein on HTLV-1 5’ LTR promoter activity. We have recently accumulated new results demonstrating that antisense transcripts also exist in HTLV-2, -3 and -4. Furthermore, our data have confirmed the existence of encoded proteins from these antisense transcripts (termed antisense proteins of HTLVs or APHs. APHs are also involved in the down-regulation of Tax-dependent viral transcription. In this review, we will focus on the different molecular mechanisms used by HBZ and APH-2 to control viral expression. While HBZ interacts with CREB through its basic zipper domain, APH-2 binds to this cellular factor through a five amino acid motif localized in its carboxyl terminus. Moreover, unlike APH-2, HBZ possesses an N-terminal activation domain that also contributes to the inhibition of the viral transcription by interacting with the KIX domain of p300/CBP. On the other hand, HBZ was found to induce T-cell proliferation while APH-2 was unable to promote such proliferation. Interestingly, HTLV-2 has not been causally linked to human T-cell leukemia, while HTLV-1 is responsible for the development of the Adult T-cell Leukemia/Lymphoma (ATLL. We will further discuss the possible role played by antisense proteins in the establishment of pathologies induced by viral infection.

HTLV-1 Rex: the courier of viral messages, making use of the host vehicle

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Kazumi eNakano

2012-09-01

Full Text Available The human T-cell leukemia virus type 1 (HTLV-1 is a retrovirus causing an aggressive T-cell malignancy, adult T-cell leukemia (ATL. Although HTLV-1 has a compact RNA genome, it has evolved elaborate mechanisms to maximize its coding potential. The structural proteins Gag, Pro, and Pol are encoded in the unspliced form of viral mRNA, whereas the Env protein is encoded in singly spliced viral mRNA. Regulatory and accessory proteins, such as Tax, Rex, p30II, p12, and p13, are translated only from fully spliced mRNA. For effective viral replication, translation from all forms of HTLV-1 transcripts has to be achieved in concert, although unspliced mRNA are extremely unstable in mammalian cells. It has been well recognized that HTLV-1 Rex enhances the stability of unspliced and singly spliced HTLV-1 mRNA by promoting nuclear export and thereby, removing them from the splicing site. Rex specifically binds to the highly structured Rex responsive element (RxRE located at the 3′ end of all HTLV-1 mRNA. Rex then binds to the cellular nuclear exporter, CRM1, via its nuclear export signal domain and the Rex-viral transcript complex is selectively exported from the nucleus to the cytoplasm for effective translation of the viral proteins. Yet, the mechanisms by which Rex inhibits the cellular splicing machinery and utilizes the cellular pathways beneficial to viral survival in the host cell have not been fully explored. Furthermore, physiological impacts of Rex against homeostasis of the host cell via interactions with numerous cellular proteins have been largely left uninvestigated. In this review, we focus on the biological importance of HTLV-1 Rex in the HTLV-1 life cycle by following the historical path in the literature concerning this viral post-transcriptional regulator from its discovery to this day. In addition, for future studies, we discuss recently discovered aspects of HTLV-1 Rex as a post-transcriptional regulator and its use in host cellular

Cis-drivers and trans-drivers of bovine leukemia virus oncogenesis.

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Safari, Roghaiyeh; Hamaidia, Malik; de Brogniez, Alix; Gillet, Nicolas; Willems, Luc

2017-10-01

The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the mechanisms of oncogenesis are still largely unknown, there is clear experimental evidence showing that BLV infection drastically modifies the pattern of gene expression of the host cell. This alteration of the transcriptome in infected B-lymphocytes results first, from a direct activity of viral proteins (i.e. transactivation of gene promoters, protein-protein interactions), second, from insertional mutagenesis by proviral integration (cis-activation) and third, from gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous immune response that indirectly modifies gene transcription in other cell types (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle, insertional mutagenesis and microRNA-associated RNA interference can modify the cell fate without inducing an antiviral immunity. Despite a tight control by the immune response, the permanent attempts of the virus to replicate ultimately induce mutations in the infected cell. Accumulation of these genomic lesions and Darwinian selection of tumor clones are predicted to lead to cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Discordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.

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Twizere, J C; Kerkhofs, P; Burny, A; Portetelle, D; Kettmann, R; Willems, L

2000-11-01

Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions

Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

International Nuclear Information System (INIS)

Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

1982-01-01

The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies

Phosphorylation regulates human T-cell leukemia virus type 1 Rex function

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Ward Michael

2009-11-01

Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 is a pathogenic complex deltaretrovirus, which is the causative agent of adult T-cell leukemia/lymphoma (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to the structural and enzymatic viral gene products, HTLV-1 encodes the positive regulatory proteins Tax and Rex along with viral accessory proteins. Tax and Rex proteins orchestrate the timely expression of viral genes important in viral replication and cellular transformation. Rex is a nucleolar-localizing shuttling protein that acts post-transcriptionally by binding and facilitating the export of the unspliced and incompletely spliced viral mRNAs from the nucleus to the cytoplasm. HTLV-1 Rex (Rex-1 is a phosphoprotein and general protein kinase inhibition correlates with reduced function. Therefore, it has been proposed that Rex-1 function may be regulated through site-specific phosphorylation. Results We conducted a phosphoryl mapping of Rex-1 over-expressed in transfected 293 T cells using a combination of affinity purification and liquid chromatography tandem mass spectrometry. We achieved 100% physical coverage of the Rex-1 polypeptide and identified five novel phosphorylation sites at Thr-22, Ser-36, Thr-37, Ser-97, and Ser-106. We also confirmed evidence of two previously identified residues, Ser-70 and Thr-174, but found no evidence of phosphorylation at Ser-177. The functional significance of these phosphorylation events was evaluated using a Rex reporter assay and site-directed mutational analysis. Our results indicate that phosphorylation at Ser-97 and Thr-174 is critical for Rex-1 function. Conclusion We have mapped completely the site-specific phosphorylation of Rex-1 identifying a total of seven residues; Thr-22, Ser-36, Thr-37, Ser-70, Ser-97, Ser-106, and Thr-174. Overall, this work is the first to completely map the phosphorylation sites in Rex-1 and provides important insight into

Monocytic leukemias.

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Shaw, M T

1980-05-01

The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

Properties of murine leukemia viruses produced by leukemic cells established from NIH Swiss mice with radiation-induced leukemia

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Okumoto, Masaaki; Nishikawa, Ryosuke; Takamori, Yasuhiko; Iwai, Yoshiaki; Iwai, Mineko [Radiation Center of Osaka Prefecture, Sakai (Japan); Imai, Shunsuke; Morimoto, Junji; Tsubura, Yoshihiko

1984-06-01

Three leukemic cell lines, designated NIH-RL1, NIH-RL2 and NFS-RL1, were established from spleen and thymuses of NIH Swiss and NFS mice with radiation-induced leukemia. The culture fluids of these cell lines contained RNA-dependent DNA polymerase (RDDP) activities associated with particles of buoyant density of 1.15-1.17 (g/cm/sup 3/). The divalent cation reqirement of these enzymes was characteristic for that of murine leukemia viruses. In competition radioimmunoassay, a major core protein, p30, was detected in culture fluid of each leukemic cell line. Competition curves of viral p30 produced by these cell lines revealed that these viruses were very similar to those of xenotropic viruses of NZB mice. These viruses were undetectable both by XC plaque assay using SC-1 cells as an indicator cell, and by mink S/sup +/L/sup -/ focus induction assay. These viruses also lacked productive infectivity to mink lung cells (CCL-64), and were nononcogenic in syngeneic mice when the viruses were intrathymically inoculated.

Murine leukemia virus (MLV replication monitored with fluorescent proteins

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Bittner Alexandra

2004-12-01

Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Wustrow, T.P.; Good, R.A.

1985-01-01

Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study

Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

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Oka, Takashi; Sato, Hiaki; Ouchida, Mamoru; Utsunomiya, Atae; Yoshino, Tadashi

2011-01-01

Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed

Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

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Oka, Takashi, E-mail: oka@md.okayama-u.ac.jp [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Sato, Hiaki [Department of Medical Technology, Graduate School of Health Science, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Ouchida, Mamoru [Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Utsunomiya, Atae [Department of Hematology, Imamura Bun-in Hospital, 11-23 Kamoike Shinnmachi, Kagoshima, 890-0064 (Japan); Yoshino, Tadashi [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan)

2011-02-04

Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed.

Viral findings in adult hematological patients with neutropenia.

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Lars Ohrmalm

Full Text Available BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159 were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22% and NPA (18% with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL (p<0.01 and patients with fever (p<0.001 were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.

Direct inhibition of RNAse T2 expression by the HTLV-1 viral protein Tax.

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Polakowski, Nicholas; Han, Hongjin; Lemasson, Isabelle

2011-08-01

Adult T-cell leukemia (ATL) is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1) infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP) assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.

Direct Inhibition of RNAse T2 Expression by the HTLV-1 Viral Protein Tax

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Isabelle Lemasson

2011-08-01

Full Text Available Adult T-cell leukemia (ATL is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1 infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.

AKT capture by feline leukemia virus.

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Kawamura, Maki; Umehara, Daigo; Odahara, Yuka; Miyake, Ariko; Ngo, Minh Ha; Ohsato, Yoshiharu; Hisasue, Masaharu; Nakaya, Masa-Aki; Watanabe, Shinya; Nishigaki, Kazuo

2017-04-01

Oncogene-containing retroviruses are generated by recombination events between viral and cellular sequences, a phenomenon called "oncogene capture". The captured cellular genes, referred to as "v-onc" genes, then acquire new oncogenic properties. We report a novel feline leukemia virus (FeLV), designated "FeLV-AKT", that has captured feline c-AKT1 in feline lymphoma. FeLV-AKT contains a gag-AKT fusion gene that encodes the myristoylated Gag matrix protein and the kinase domain of feline c-AKT1, but not its pleckstrin homology domain. Therefore, it differs structurally from the v-Akt gene of murine retrovirus AKT8. AKT may be involved in the mechanisms underlying malignant diseases in cats.

Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

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F. Azevedo-Silva

2010-03-01

Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

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Amanda R. Panfil

2015-12-01

Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL. This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5 on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.

Juvenile Myelomonocytic Leukemia

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... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

Radiogenic leukemia revisited

International Nuclear Information System (INIS)

Moloney, W.C.

1987-01-01

Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x-ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans

Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia.

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Hakim, Hana; Dallas, Ronald; Zhou, Yinmei; Pei, Dequing; Cheng, Cheng; Flynn, Patricia M; Pui, Ching-Hon; Jeha, Sima

2016-03-01

Knowledge regarding the incidence, clinical course, and impact of respiratory viral infections in children with acute lymphoblastic leukemia (ALL) is limited. A retrospective cohort of patients with newly diagnosed ALL who were treated on the Total Therapy XVI protocol at St Jude Children's Research Hospital between 2007 and 2011 was evaluated. Of 223 children, 95 (43%) developed 133 episodes of viral acute respiratory illness (ARI) (incidence, 1.1 per 1000 patient-days). ARI without viral etiology was identified in 65 patients (29%) and no ARI was detected in 63 patients (28%). There were no significant associations noted between race, sex, age, or ALL risk group and the development of ARI. Children receiving induction chemotherapy were found to be at the highest risk of viral ARI (incidence, 2.3 per 1000 patient-days). Influenza virus was the most common virus (38%) followed by respiratory syncytial virus (33%). Of 133 episodes of viral ARI, 61% of patients were hospitalized, 26% experienced a complicated course, 80% had their chemotherapy delayed, and 0.7% of patients died. Twenty-four patients (18%) developed viral lower respiratory tract infections (LRTI), 5 of whom (21%) had complications. Patients with viral LRTI had a significantly lower nadir absolute lymphocyte count; were sicker at the time of presentation; and were more likely to have respiratory syncytial virus, to be hospitalized, and to have their chemotherapy delayed for longer compared with those with viral upper respiratory tract infections. Despite the low incidence of viral ARI in children with ALL, the associated morbidity, mortality, and delay in chemotherapy remain clinically significant. Viral LRTI was especially associated with high morbidity requiring intensive care-level support. Cancer 2016;122:798-805. © 2015 American Cancer Society. © 2015 American Cancer Society.

and Vernonia Amygdalina

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ADOWIE PERE

The result showed that there was a reduction (p<0.05) in the blood glucose level of ..... Method: Enzymatic method for estimating amylase activity by. Rauscher and Buelow (Rauscher, et al., 1982;. Rauscher ..... Effect of honey as partial sugar.

SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

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2013-01-10

Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

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Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-AL...

Leukemia

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Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

Are endogenous feline leukemia viruses really endogenous?

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Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

2011-10-15

Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

Chronic myelogenous leukemia (CML)

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CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

The virion RNA species of the Kirsten murine sarcoma-leukemia virus complex released from a clonally related series of mouse cells

International Nuclear Information System (INIS)

Clewley, J.P.; Avery, R.J.

1982-01-01

We have characterized the virion RNA species of Kirsten sarcoma (KiSV) and Kirsten leukemia (KiLV) viruses released from a clonally related series of mouse cells (14). We have identified the KiLV and KiSV genome RNAs. In addition to the viral RNA species we find large amounts of a virus-like RNA (VL30 RNA), which is heterogeneous and shows variability in its expression. The amount of VL30 RNA in virions does not correlate with the state of transformation of the cells releasing the virus or the ability of the virus to transform other cells. Characterization of RNA rescued from non-producer cells has revealed a sarcoma virus (KiSVsub(SB3) with an oligonucleotide fingerprint different from that of a standard KiSV RNA, suggesting that it has lost some viral sequences. The oligonucleotide fingerprints of KiLV and VL30 RNAs are distinct from each other and from those reported for other murine leukemia virus RNAs. (Author)

Chronic Myelogenous Leukemia

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Chronic myelogenous leukemia Overview Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the blood cells. The term "chronic" in chronic myelogenous leukemia indicates that this cancer ...

Chronic neutrophilic leukemia.

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Bredeweg, Arthur; Burch, Micah; Krause, John R

2018-01-01

Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

Effect of radiation on normal hematopoiesis and on viral induced cancers of the hematopoietic system. Technical progress report, August 1, 1974--May 1, 1975

International Nuclear Information System (INIS)

Okunewick, J.P.

1975-01-01

Studies carried out during the above period on viral leukemia have conclusively shown that the pluripotent hematopoietic colony forming stem cell (CFU-S) is a target cell for the leukemia virus. Treatment of this cell population with antiserum prepared in syngeneic mice against the disease resulted in inactivation of up to 50 percent of the CFU-S obtained from the spleens of viral leukemic mice. At the same time, normal serum had no effect on these cells, nor did the antiserum have any effect on normal CFU-S. Data indicated that a considerable time delay, on the order of a week, preceded the expression of the viral antigen in the leukemic CFU-S, but that it could be seen at all times after that up to the terminal point of the disease. We examined the effect of the virus on DNA synthesis (S-phase cells) in the CFU-S immediately after virus injection. The results showed that a doubling of the number of cells in S could be seen as early as four hours after introduction of the virus into the animal. Studies with ethidium bromide, an inhibitor of viral reverse transcriptase, were found to be in agreement with this observation. When given to viral leukemic animals in combination with fractionated exposure to x-ray, the data suggested that ethidium bromide did act to extend survival somewhat, but not much over that seen through the use of x-ray alone

Kelainan Hemostasis pada Leukemia

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Zelly Dia Rofinda

2012-09-01

Full Text Available AbstrakLatar belakang: Leukemia adalah penyakit keganasan pada jaringan hematopoietik yang ditandai denganpenggantian elemen sumsum tulang normal oleh sel darah abnormal atau sel leukemik. Salah satu manifestasi klinisdari leukemia adalah perdarahan yang disebabkan oleh berbagai kelainan hemostasis.Kelainan hemostasis yang dapat terjadi pada leukemia berupa trombositopenia, disfungsi trombosit,koagulasi intravaskuler diseminata, defek protein koagulasi, fibrinolisis primer dan trombosis. Patogenesis danpatofosiologi kelainan hemostasis pada leukemia tersebut terjadi dengan berbagai mekanisme.Kata kunci: leukemia, kelainan hemostasisAbstractBackground: AbstractLeukemia is a malignancy of hematopoietic tissue which is characterized bysubstituted of bone marrow element with abnormal blood cell or leukemic cell. One of clinical manifestation ofleukemia is bleeding that is caused by several hemostasis disorders.Hemostasis disorders in leukemia such asthrombocytopenia, platelet dysfunction, disseminated intravascular coagulation, coagulation protein defect, primaryfibrinolysis and thrombosis. Pathogenesis and pathophysiology of thus hemostasis disorders in leukemia occur withdifferent mechanism.Keywords: leukemia, hemostasis disorder

HTLV-1 Alters T Cells for Viral Persistence and Transmission

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Azusa Tanaka

2018-03-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ, are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5′ long terminal repeat (LTR in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases. HBZ is known to function in both protein form and mRNA form, and both forms play an important role in the oncogenic process of HTLV-1. HBZ protein has a variety of functions, including the suppression of apoptosis, the promotion of proliferation, and the impairment of anti-viral activity, through the interaction with several host cellular proteins including p300/CBP, Foxp3, and Foxo3a. These functions dramatically modify the transcriptional profiling of host T cells. HBZ mRNA also promotes T cell proliferation and viability. HBZ changes infected T cells to CCR4+TIGIT+CD4+ effector/memory T cells. This unique immunophenotype enables T cells to migrate into various organs and tissues and to survive in vivo. In this review, we summarize how HBZ hijacks the transcriptional networks and immune systems of host T cells to contribute to HTLV-1 pathogenesis on the basis of recent new findings about HBZ and tax.

Atypical Chronic Myelogenous Leukemia

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... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

Barriers to Infection of Human Cells by Feline Leukemia Virus: Insights into Resistance to Zoonosis.

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Terry, Anne; Kilbey, Anna; Naseer, Asif; Levy, Laura S; Ahmad, Shamim; Watts, Ciorsdaidh; Mackay, Nancy; Cameron, Ewan; Wilson, Sam; Neil, James C

2017-03-01

The human genome displays a rich fossil record of past gammaretrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro Feline leukemia viruses (FeLVs) rank high on this list, but neither domestic nor workplace exposure has been associated with detectable serological responses. Nonspecific inactivation of gammaretroviruses by serum factors appears insufficient to explain these observations. To investigate further, we explored the susceptibilities of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines but was also a feature of nontransformed keratinocytes and lung fibroblasts. Cells of hematopoietic origin were generally less permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in nonpermissive cells. FeLV-B was subject to G→A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in nonpermissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV. IMPORTANCE Domestic exposure to gammaretroviruses such as feline leukemia viruses (FeLVs) occurs worldwide, but the basis of human resistance to infection remains incompletely understood. The potential threat is evident from the human genome sequence, which reveals many past epidemics of gammaretrovirus infection, and from recent cross-species jumps of gammaretroviruses from rodents to primates and marsupials. This study examined resistance to infection at the cellular level with the most

Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

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Simone Santana Viana

2012-01-01

Full Text Available OBJECTIVE: To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. METHODS: Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses and the results were compared to the data of 33 healthy children matched for gender, age and social class. RESULTS: After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. CONCLUSION: Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status.

Characterization of tumour virus proteins, 2

International Nuclear Information System (INIS)

Higuchi, T.

1977-01-01

The structural protein in murine tumour virus P30 has been measured by radioiummunoassay. The titer of each serum was determined by using as antigen the purified Rauscher viral protein labeled with 125 iodine. Standard competition curve was constructed in order to determine the equivalent of protein to inhibit the precipitation reaction under limited antibody concentration. Competition by purified Kirsten virus suspension normal rat kidney cells, transformed-productive and transformed non-productive cells were measured in homologous and heterologous systems [pt

Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity.

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Kannagi, Mari; Hasegawa, Atsuhiko; Kinpara, Shuichi; Shimizu, Yukiko; Takamori, Ayako; Utsunomiya, Atae

2011-04-01

Human T-cell leukemia virus type 1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-specific T-cell responses elicit antitumor and antiviral effects in experimental models, and are considered to be one of the most important determinants of the disease manifestation, since they are activated in HAM/TSP but not in ATL patients. The combination of low T-cell responses and elevated HTLV-1 proviral loads are features of ATL, and are also observed in a subpopulation of HTLV-1 carriers at the asymptomatic stage, suggesting that these features may be underlying risk factors. These risks may potentially be reduced by vaccination to activate HTLV-1-specific T-cell responses. HAM/TSP and ATL patients also differ in their levels of HTLV-1 mRNA expression, which are generally low in vivo but slightly higher in HAM/TSP patients. Our recent study indicated that viral expression in HTLV-1-infected T-cells is suppressed by stromal cells in culture through type-I IFNs. The suppression was reversible after isolation from the stromal cells, mimicking a long-standing puzzling phenomenon in HTLV-1 infection where the viral expression is very low in vivo and rapidly induced in vitro. Collectively, HTLV-1 is controlled by both acquired and innate immunity in vivo: HTLV-1-specific T-cells survey infected cells, and IFNs suppress viral expression. Both effects would contribute to a reduction in viral pathogenesis, although they may potentially influence or conflict with one another. The presence of double control systems for HTLV-1 infection provides a new concept for understanding the pathogenesis of HTLV-1-mediated malignant and inflammatory diseases. © 2011 Japanese Cancer Association.

Retroviral DNA integration: viral and cellular determinants of target-site selection.

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Mary K Lewinski

2006-06-01

Full Text Available Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV integrates preferentially within active transcription units, whereas murine leukemia virus (MLV integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN coding region into HIV (to make HIVmIN caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb, and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.

Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

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Chechik, B E; Jason, J; Shore, A; Baker, M; Dosch, H M; Gelfand, E W

1979-12-01

Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

The leukemias: Epidemiologic aspects

International Nuclear Information System (INIS)

Linet, M.S.

1984-01-01

Particularly geared to physicians and cancer researchers, this study of the epidemiology and etiology of leukemia analyzes the four major leukemia subtypes in terms of genetic and familial determinant factors and examines the incidence, distribution and frequency of reported leukemia clusters. Linet discusses the connection between other types of malignancies, their treatments, and the subsequent development of leukemia and evaluates the impact on leukemia onset of such environmental factors as radiation therapy, drugs, and occupational hazards

Murine and human leukemias.

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Burchenal, J H

1975-01-01

Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).

Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa.

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Hofmann-Lehmann, R; Fehr, D; Grob, M; Elgizoli, M; Packer, C; Martenson, J S; O'Brien, S J; Lutz, H

1996-09-01

While viral infections and their impact are well studied in domestic cats, only limited information is available on their occurrence in free-ranging lions. The goals of the present study were (i) to investigate the prevalence of antibodies to feline calicivirus (FCV), herpesvirus (FHV), coronavirus (FCoV), parvovirus (FPV), and immunodeficiency virus (FIV) and of feline leukemia virus (FeLV) antigen in 311 serum samples collected between 1984 and 1991 from lions inhabiting Tanzania's national parks and (ii) to evaluate the possible biological importance and the interrelationship of these viral infections. Antibodies to FCV, never reported previously in free-ranging lions, were detected in 70% of the sera. In addition, a much higher prevalence of antibodies to FCoV (57%) was found than was previously reported in Etosha National Park and Kruger National Park. Titers ranged from 25 to 400. FeLV antigen was not detectable in any of the serum samples. FCoV, FCV, FHV, and FIV were endemic in the Serengeti, while a transient elevation of FPV titers pointed to an outbreak of FPV infection between 1985 and 1987. Antibody titers to FPV and FCV were highly prevalent in the Serengeti (FPV, 75%; FCV, 67%) but not in Ngorongoro Crater (FPV, 27%; FCV, 2%). These differences could be explained by the different habitats and biological histories of the two populations and by the well-documented absence of immigration of lions from the Serengeti plains into Ngorongoro Crater after 1965. These observations indicate that, although the pathological potential of these viral infections seemed not to be very high in free-ranging lions, relocation of seropositive animals by humans to seronegative lion populations must be considered very carefully.

Inheritance of leukemia in humans

International Nuclear Information System (INIS)

Kamada, Nanao

1991-01-01

Since Gardner et al. reported an increased incidence of leukemia among children of workers of a nuclear reactor in Sellafield, UK, there have been a number of discussions on the possibility of increased incidence of leukemia among children born from parents exposed to radiation or chemical agents. In this present paper, apart from the leukemia incidence in children from atomic bomb survivors which was discussed by Dr. Yoshimoto, familial leukemia, i.e., a cluster of leukemia among family members within four genetic relations, was discussed with special reference to the age distribution, type of leukemia and consanguinity. Leukemia in twin and leukemias in individuals with congenital anomalies with or without chromosome abnormalities were also discussed. (author)

Mutational library analysis of selected amino acids in the receptor binding domain of envelope of Akv murine leukemia virus by conditionally replication competent bicistronic vectors

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Bahrami, Shervin; Jespersen, Thomas; Pedersen, Finn Skou

2003-01-01

The envelope protein of retroviruses is responsible for viral entry into host cells. Here, we describe a mutational library approach to dissect functional domains of the envelope protein involving a retroviral vector, which expresses both the envelope protein of Akv murine leukemia virus (MLV) an...

Effects of chemical carcinogens of hemopoiesis, immunopoiesis and viral oncogenesis. Technical progress report, December 1, 1977--September 30, 1978. [Mechanisms of potentiation of viral leukemogenesis by MMS, benzopyrene, and DMBA

Energy Technology Data Exchange (ETDEWEB)

OKunewick, J.P.; Raikow, R.B.; Meredith, R.F.

1978-10-01

During the past year we have concentrated on defining the circumstances under which methyl methanesulfonate (MMS), benzo(a) pyrene (BP), and 7,12-dimethylbenz(a)anthracene (DMBA) interact with Friend virus (FLV) to produce leukemia. The optimum scheduling for each and also the effective dose levels of the chemicals have been partially determined. There are at least three critical factors which govern whether or not a leukemogenic interaction can be shown between the chemical agents and the virus. These are chemical dose, virus dose, and their relative time of administration. The most critical of these is virus dose. The optimum virus dose is that which results in between 25 and 40% incidence of leukemia within 40 days after virus infection when virus is given alone. The chemical carcinogens have a lower dose threshold, below which no significant potentiating effect can be observed. The only upper limit would appear to be acute drug toxicity. The third element, timing, is equally critical and varies according to the chemical. This variation may reflect different mechanisms of action by the chemical agents and/or different pharmacology. Data on the effects of MMS, BP, and DMBA on the immune system have indicated that the viral enhancement is probably not dependent on this function. Further enhancement of the potentiation of viral leukemogenesis was observed using benzo(a)pyrene and caffeine, indicating that the inhibition by caffeine of DNA repair may be an important factor in virus potentiation. (ERB)

Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in Japanese chronic lymphocytic leukemia cases

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Imajoh Masayuki

2012-06-01

Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9, another lymphotropic polyomavirus, in Japanese CLL cases. Findings We found that 9/27 CLL cases (33.3 % were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. Conclusions This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.

[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission].

Science.gov (United States)

Richard, C; Iriondo, A; Baro, J; Conde, E; Hermosa, V; Alsar, M J; Gómez Casares, M T; Muruzabal, M J; Pérez Encinas, M; Zubizarreta, A

1990-09-22

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.

Occupation and leukemia in Nordic countries

DEFF Research Database (Denmark)

Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar

2012-01-01

We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

Congenital Leukemia in Down's syndrome

International Nuclear Information System (INIS)

Iqbal, W.; Khan, F.; Muzaffar, M.; Khan, U. A.; Rehman, M. U.; Khan, M. A.; Bari, A.

2006-01-01

Congenital Leukemia is a condition and often associated with fatal outcome/sup 1/. Most of the neonatal cases reported have acute non-lymphoblastic leukemia, in contrast to the predominance of acute lymphoblastic leukemia found in later childhood. congenital leukemia is occasionally associated with number of congenital anomalies and with chromosomal disorders such as Down's syndrome. Subtle cytogenetic abnormalities may occur more commonly in the affected infants and their parents, when studied with newer cytogenetic techniques/sup 2/. Inherent unstable hematopoieses resulting from chromosomal aberration in children with Downs's syndrome can present with transient myeloproliferative disorder, mimicking leukemia which undergoes spontaneous recovery/sup 3/. Only few cases of congenital leukemia with Downs syndrome, presented as congenital leukemia. (author)

Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

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Mueller Nancy

2005-10-01

Full Text Available Abstract Background Human T-cell leukemia virus type I (HTLV-I causes adult T-cell leukemia (ATL after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. Results The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. Conclusion These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.

Atomic bomb and leukemia

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Ichimaru, M; Tomonaga, M; Amenomori, T; Matsuo, T [Nagasaki Univ. (Japan). School of Medicine

1991-12-01

Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for chronic myelogenous leukemia (CML) in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5{approx}0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of acute myeloid leukemia (AML) subtypes by French-American-British classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors. (author).

Atomic bomb and leukemia

International Nuclear Information System (INIS)

Ichimaru, M.; Tomonaga, M.; Amenomori, T.; Matsuo, T.

1991-01-01

Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for chronic myelogenous leukemia (CML) in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5∼0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of acute myeloid leukemia (AML) subtypes by French-American-British classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors. (author)

Reanalysis of atomic bomb survivors' leukemia based on the recent classification for leukemias

International Nuclear Information System (INIS)

Matsuo, Tatsuki; Tomonaga, Masao.

1990-01-01

Four hundred and ninety-three A-bomb survivors developing leukemia, who had been exposed within 9,000 m from the hypocenter, were entered on the study for reanalysis of their disease based on the new classification. Chronic myelocytic leukemia (CML) showed the highest concordance rate (95%) between the previous and new classifications. For 10 survivors previously diagnosed as having chronic lymphocytic leukemia (CLL), a new classification diagnosed CLL as well in 3 and adult T-cell leukemia in the other 7. None of the A-bomb survivors exposed to one Gy or more had subtype M3 of acute myelocytic leukemia (AML), although the exposed group had almost the same distribution pattern of AML subtypes as the naturally induced leukemic group. The incidence of CML was significantly lower than that of AML in Nagasaki A-bomb survivors. As A-bomb survivors were older at the time of A-bombing, the relative risk of acute lymphoblastic leukemia (ALL) was decreased; that of CML and other types of leukemia was increased. An increased relative risk of ALL and CML tended to be associated with larger doses. A significantly shortened interval between A-bomb exposure and the development of leukemia was also associated with larger doses. (N.K.)

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.

Science.gov (United States)

Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

2017-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2 , and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

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Shi Hao Tan

2017-09-01

Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs, which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia

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Pritish K Bhattacharyya

2013-01-01

Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia′s. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and less commonly lymphoid. Association between CLL and myeloid malignancies (CML, acute myeloid leukemia and MDS, myelodysplastic syndrome is rare. In literature documenting CLL and CML in same patients, occur either simultaneously or CML is preceded by CLL.

Experimental studies of leukemia

International Nuclear Information System (INIS)

Yokoro, Kenjiro

1977-01-01

Mouse leukemia, especially the relationship between that and endogenous type-C RNA virus (murine leukemia virus, MLV), was generally discussed centering around the recent findings and reports. Correlation of carcinogenesis due to x-rays and carcinogens with the occurrence of MLV, the relationship of total body fractionated x-ray irradiation and successive acellular transmission by the neonatal inoculation with MLV, and the relationship between N-nitrosobutylurea or N-nitrosoethylurea and MLV were discussed. The relationship between the occurrence of MLV and thymus or spleen was also discussed. Biotic differences in mice and rats, the relationship between MLV the organotropism of MLV and provocation of leukemia, the directivity of MLV to thymus and the etiologic correlation of rat leukemia or mouse leukemia with MLV were mentioned. (Ichikawa, K.)

Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

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Strasak Alexander

2009-06-01

Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

Extramedullary leukemia in children with acute myeloid leukemia

DEFF Research Database (Denmark)

Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

2017-01-01

BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

Thrombopoietin/MPL signaling confers growth and survival capacity to CD41-positive cells in a mouse model of Evi1 leukemia.

Science.gov (United States)

Nishikawa, Satoshi; Arai, Shunya; Masamoto, Yosuke; Kagoya, Yuki; Toya, Takashi; Watanabe-Okochi, Naoko; Kurokawa, Mineo

2014-12-04

Ecotropic viral integration site 1 (Evi1) is a transcription factor that is highly expressed in hematopoietic stem cells and is crucial for their self-renewal capacity. Aberrant expression of Evi1 is observed in 5% to 10% of de novo acute myeloid leukemia (AML) patients and predicts poor prognosis, reflecting multiple leukemogenic properties of Evi1. Here, we show that thrombopoietin (THPO) signaling is implicated in growth and survival of Evi1-expressing cells using a mouse model of Evi1 leukemia. We first identified that the expression of megakaryocytic surface molecules such as ITGA2B (CD41) and the THPO receptor, MPL, positively correlates with EVI1 expression in AML patients. In agreement with this finding, a subpopulation of bone marrow and spleen cells derived from Evi1 leukemia mice expressed both CD41 and Mpl. CD41(+) Evi1 leukemia cells induced secondary leukemia more efficiently than CD41(-) cells in a serial bone marrow transplantation assay. Importantly, the CD41(+) cells predominantly expressing Mpl effectively proliferated and survived on OP9 stromal cells in the presence of THPO via upregulating BCL-xL expression, suggesting an essential role of the THPO/MPL/BCL-xL cascade in enhancing the progression of Evi1 leukemia. These observations provide a novel aspect of the diverse functions of Evi1 in leukemogenesis. © 2014 by The American Society of Hematology.

Leukemia-associated antigens in man.

Science.gov (United States)

Brown, G; Capellaro, D; Greaves, M

1975-12-01

Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

Vorinostat in Treating Patients With Acute Myeloid Leukemia

Science.gov (United States)

2014-04-30

Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Acute Lymphocytic Leukemia

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Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

Acute Myeloid Leukemia

Science.gov (United States)

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

Chronic Lymphocytic Leukemia

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Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

Chronic Myeloid Leukemia

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Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

Progress in the leukemias

International Nuclear Information System (INIS)

Galton, D.A.G.; Spiers, A.S.D.

1971-01-01

Recent work on the epidemiology of leukemia is reviewed in relation to factors of possible etiologic importance. There is still much geographic variation in the accuracy of diagnosis, the reliability of death certification, and the provision of national registries for classifying leukemia according to cytologic type. This variation and the low incidence of all types of leukemia make difficult the recognition of potentially significant distributions or trends that might suggest the operation of environmental leukemogens and their interaction with genetically determined susceptibility. Exposure to ionizing radiation remains the only predisposing factor beyond doubt for acute and chronic granulocytic leukemia, but its exact role remains obscure. There is no evidence that radiation plays a part in the etiology of chronic lymphocytic leukemia. In the population of survivors of the Hiroshima atomic bomb explosion of 1945, the incidence of leukemia (mainly CGL), though declining in the second 10-year period, was still higher than that of Japan as a whole. The suggestion that the exposure of women to radiation could increase the likelihood of leukemia in their still unconceived children was examined by the Atomic Bomb Casualty Commission in a prospective study of 17,700 children, and no increase in the incidence of leukemia was found in the children of parents who had been heavily exposed to radiation before conception. In the 1960's a decline in the United States mortality rates for leukemia among the white population was recorded. This decline was most marked in children below age 5, and it was suggested that the decline could have resulted from a drop in the use of diagnostic radiology in pregnant women following the reports in 1956 of the Medical Research Council and the National Academy of Sciences on the biologic hazards of radiation. A similar decline in mortality was reported from Norway. (464 references) (U.S.)

Radiotherapy for leukemia in children, (1). Radiotherapy for central nervous system leukemia

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro [Maizuru National Hospital, Kyoto (Japan)

1983-07-01

Following the development of effective chemotherapy for producing remissions of acute lymphocytic leukemia (ALL), a new phenomenon has emerged in this disease--central nervous system (CNS) leukemia. CNS leukemia has become an increasingly frequent obstacle to prolongation of initial complete remission. Prophylactic irradiation of the CNS concomitant with intrathecal administration of methotrexate (IT-MTX) has proved to be effective in the reduction of CNS involvement. The purpose of this paper is to describe the results of irradiation for prevention of CNS leukemia and to discuss their implications. The patients consisted of 32 children with acute leukemia, admitted to MAIZURU National Hospital from 1966 to 1980; 22 patients of them had ALL, the others ANLL (acute non-lymphocytic leukemia). Preventive CNS therapy was started in 1974, (group A), but there was no prevention before 1974 (group B). 1. In group B, six patients was treated by therapeutic cranial irradiation, but all cases resulted in death. 2. In group A, seven patients was treated by prophylactic cranial irradiation combined with IT-MTX, and all of them have been alive without CNS relapse for 2 to 4 2/3 years after therapy. 3. In group A, none of 7 patients (0 %) relapsed CNS leukemia initially as compared to 7 (50 %) of 14 in group B, thus preventive efficacy was clear. 4. There were no severe complications attributable to the radiotherapy, with or without IT-MTX.

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

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Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

2006-08-22

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

Profile of imatinib in pediatric leukemia

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Burke MJ

2014-02-01

Full Text Available Michael J BurkeDepartment of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USAAbstract: Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI, was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+ oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.Keywords: imatinib, leukemia, lymphoblastic leukemia, chronic myeloid leukemia, pediatric

What You Need to Know about Leukemia

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... Publications Reports What You Need To Know About™ Leukemia This booklet is about leukemia. Leukemia is cancer of the blood and bone marrow ( ... This book covers: Basics about blood cells and leukemia Types of doctors who treat leukemia Treatments for ...

Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

International Nuclear Information System (INIS)

Tanaka, K.; Tanaka, H.; Kamada, N.

2003-01-01

It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

Childhood Leukemia and Primary Prevention

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Whitehead, Todd P.; Metayer, Catherine; Wiemels, Joseph L.; Singer, Amanda W.; Miller, Mark D.

2016-01-01

Leukemia is the most common pediatric cancer, affecting 3,800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia – usually before age five – and the presence at birth of “pre-leukemic” genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature – in the United States and internationally – that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the pre-conception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors – including pooled analyses from around the world and systematic reviews – is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children’s health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgement until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co

Acute Lymphocytic Leukemia

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... that may increase the risk of acute lymphocytic leukemia include: Previous cancer treatment. Children and adults who've had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased ... leukemia. Exposure to radiation. People exposed to very high ...

Fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.

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Sanggu Kim

Full Text Available Xenotropic murine leukemia virus (MLV-related virus (XMRV is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.

Decreased expression of endogenous feline leukemia virus in cat lymphomas: a case control study.

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Krunic, Milica; Ertl, Reinhard; Hagen, Benedikt; Sedlazeck, Fritz J; Hofmann-Lehmann, Regina; von Haeseler, Arndt; Klein, Dieter

2015-04-10

Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma development than uninfected cats. Furthermore, an increased exFeLV transcription has been detected in lymphomas compared to non-malignant tissues. The possible mechanisms of lymphoma development by exFeLV are insertional mutagenesis or persistent stimulation of host immune cells by viral antigens, bringing them at risk for malignant transformation. Vaccination of cats against exFeLV has in recent years decreased the overall infection rate in most countries. Nevertheless, an increasing number of lymphomas have been diagnosed among exFeLV-negative cats. Endogenous feline leukemia virus (enFeLV) is another retrovirus for which transcription has been observed in cat lymphomas. EnFeLV provirus elements are present in the germline of various cat species and share a high sequence similarity with exFeLV but, due to mutations, are incapable of producing infectious viral particles. However, recombination between exFeLV and enFeLV could produce infectious particles. We examined the FeLV expression in cats that have developed malignant lymphomas and discussed the possible mechanisms that could have induced malignant transformation. For expression analysis we used next-generation RNA-sequencing (RNA-Seq) and for validation reverse transcription quantitative PCR (RT-qPCR). First, we showed that there was no expression of exFeLV in all samples, which eliminates the possibility of recombination between exFeLV and enFeLV. Next, we analyzed the difference in expression of three enFeLV genes between control and lymphoma samples. Our analysis showed an average of 3.40-fold decreased viral expression for the three genes in lymphoma compared to control samples. The results were confirmed by RT-qPCR. There is a decreased expression of enFeLV genes in lymphomas versus control samples, which contradicts previous observations for the exFeLV. Our results suggest that a persistent stimulation of host

Myeloblastic and lymphoblastic markers in acute undifferentiated leukemia and chronic myelogenous leukemia in blast crisis.

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Shumak, K H; Baker, M A; Taub, R N; Coleman, M S

1980-11-01

Blast cells were obtained from 17 patients with acute undifferentiated leukemia and 13 patients with chronic myelogenous leukemia in blast crisis. The blasts were tested with anti-i serum in cytotoxicity tests and with antisera to myeloblastic leukemia-associated antigens in immunofluorescence tests. The terminal deoxynucleotidyl transferase (TDT) content of the blasts was also measured. Lymphoblasts react strongly with anti-i, do not react with anti-myeloblast serum, and have high levels of TDT; myeloblasts react weakly with anti-i, do not react with anti-myeloblast serum, and have very low levels of TDT. Of the 17 patients with acute undifferentiated leukemia, there were six with blasts which reacted like lymphoblasts, six with blasts which reacted like myeloblasts, and five with blasts bearing different combinations of these lymphoblastic and myeloblastic markers. Eight of the 11 patients with lymphoblastic or mixed lymphoblastic-myeloblastic markers, but only one of the six with myeloblastic markers, achieved complete or partial remission in response to therapy. Thus, in acute undifferentiated leukemia, classification of blasts with these markers may be of prognostic value. Of the 13 patients with chronic myelogenous leukemia in blast crises, the markers were concordant (for myeloblasts) in only two cases. Three of the 13 patients had TDT-positive blasts, but the reactions of these cells with anti-i and with anti-myeloblast serum differed from those seen with lymphoblasts from patients with acute lymphoblastic leukemia. Although the cell involved in "lymphoid" blast crisis of chronic myelogenous leukemia is similar in many respects to that involved in acute lymphoblastic leukemia, these cells are not identical.

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

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Jakubowski Ann A

2009-12-01

Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia

OpenAIRE

Sinem Civriz Bozdag; Sinem Namdaroglu; Omur Kayikci; Gülsah Kaygusuz; Itir Demiriz; Murat Cinarsoy; Emre Tekgunduz; Fevzi Altuntas

2013-01-01

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

Esterase reactions in acute myelomonocytic leukemia.

Science.gov (United States)

Kass, L

1977-05-01

Specific and nonspecific esterase reactions of bone marrow cells from 14 patients with untreated acute myelomonocytic leukemia and six patients with acute histiomonocytic leukemia were examined. The technic for esterase determination permitted simultaneous visualization of both esterases on the same glass coverslip containing the marrow cells. In cases of acute histiomonocytic leukemia, monocytes, monocytoid hemohistioblasts and undifferentiated blasts stained intensely positive for nonspecific esterase, using alpha-naphthyl acetate as the substrate. No evidence of specific esterase activity using naphthol ASD-chloroacetate as the substrate and fast blue BBN as the dye coupler was apparent in these cells. In all of the cases of acute myelomonocytic leukemia, both specific and nonspecific esterases were visualized within monocytes, monocytoid cells, and granulocytic cells that had monocytoid-type nuclei. Nonspecific esterase activity was not observed in polymorphonuclear leukocytes in cases of myelomonocytic leukemia. The results support a current viewpoint that acute myelomonocytic leukemia may be a variant of acute myeloblastic leukemia, and that cytochemically, many of the leukemic cells in myelomonocytic leukemia share properties of both granulocytes and monocytes.

Radioinduced leukemia. An introduction to the study of experimental leukemia in mice

International Nuclear Information System (INIS)

Baudon, P.P.

1974-01-01

This thesis attempts to gain insight into any mechanisms involved in the onset of irradiation-induced leukemia in mice, then to show up the presence of a virus in the same animals. Concerning the mechanisms of radio-induced leukemias the pathogenic factors according to Kaplan are analysed: role of the thymus and cell mutation theory; lymphoid leukemias of extra-thymic origin; leukemogenesis co-factor; inhibiting action of the bone narrow. Evidence of the virus in mice was obtained by the use of electron microscopy, by inoculation. The contribution of experimental leukemia research is analysed, especially as it affects the therapeutic aspect. It is shown that in spite of setbacks in the most recent research on man, therapeutic trials on animals should be viewed from the angle of imminent human applications [fr

Leukemia, multiple myeloma, and malignant lymphoma

International Nuclear Information System (INIS)

Ichimaru, M.; Ishimaru, T.; Ohkita, T.

1986-01-01

Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20-59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM

Leukemia, multiple myeloma, and malignant lymphoma

International Nuclear Information System (INIS)

Ichimaru, Michito; Ohkita, Takeshi; Ishimaru, Toranosuke.

1986-01-01

Excess risk of leukemia among atomic bomb (A-bomb) survivors increased with radiation dose in Hiroshima and Nagasaki. The incidence of all types of leukemia, except chronic lymphocytic leukemia, has increased among A-bomb survivors. However, chronic myelogenous leukemia (CML) is thought to be the most characteristic type of the A-bomb induced leukemias. The highest risk of leukemia among A-bomb survivors was recognized in 1951 and has not yet disappeared in survivors in Hiroshima. Excess risk of leukemia in the younger age at time of bomb (ATB) groups appeared early; however, in the older age ATB groups it appeared much later especially among Hiroshima survivors. In both cities the effect of radiation exposure on the occurrence of CML was more clearly observable in the younger age ATB groups and occurred more frequently in Hiroshima. Leukemia among individuals exposed in utero and children of A-bomb survivors has not increased significantly. The relationship between radiation induced leukemia and chromosome abnormalities is discussed. Twenty years after the A-bomb, the risk of multiple myeloma (MM) increased among survivors aged 20 - 59 years ATB. Non-Hodgkin's malignant lymphoma also increased among A-bomb survivors and showed roughly the same tendency as MM. (author)

Acute Lymphoblastic Leukemia (ALL) (For Parents)

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... Staying Safe Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) What's in this article? About Leukemia Causes ...

Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

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Bahareh Pezeshkian

Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

How Is Chronic Myeloid Leukemia Diagnosed?

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... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Chimeras of receptors for gibbon ape leukemia virus/feline leukemia virus B and amphotropic murine leukemia virus reveal different modes of receptor recognition by retrovirus

DEFF Research Database (Denmark)

Pedersen, Lene; Johann, Stephen V; van Zeijl, Marja

1995-01-01

Glvr1 encodes the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related gene Glvr2 encodes the human receptor for amphotropic murine leukemia viruses (A-MLVs). The two proteins are 62% identical in their amino acid sequences...

Apparent feline leukemia virus-induced chronic lymphocytic leukemia and response to treatment.

Science.gov (United States)

Kyle, Kristy N; Wright, Zachary

2010-04-01

Chylothorax secondary to chronic lymphocytic leukemia (CLL) was diagnosed in a feline leukemia virus (FeLV)-positive 8-year-old castrated male domestic shorthair feline. The leukemia resolved following therapy with chlorambucil, prednisone, cyclophosphamide, doxorubicin, and lomustine. To our knowledge, this is the first reported case of CLL in an FeLV-positive cat. Although a causative relationship cannot be proven, patients diagnosed with either disease may benefit from diagnostics to rule out the presence of the other concurrent condition. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus

International Nuclear Information System (INIS)

Iki, Shigeo; Yokota, Shin-ichi; Okabayashi, Tamaki; Yokosawa, Noriko; Nagata, Kyosuke; Fujii, Nobuhiro

2005-01-01

The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection

Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

Science.gov (United States)

2017-03-27

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

Chemical exposure and leukemia clusters

International Nuclear Information System (INIS)

Cartwright, R.A.

1992-01-01

This paper draws attention to the heterogeneous distribution of leukemia in childhood and in adults. The topic of cluster reports and generalized clustering is addressed. These issues are applied to what is known of the risk factor for both adult and childhood leukemia. Finally, the significance of parental occupational exposure and childhood leukemia is covered. (author). 23 refs

Sequence analysis of Leukemia DNA

Science.gov (United States)

Nacong, Nasria; Lusiyanti, Desy; Irawan, Muhammad. Isa

2018-03-01

Cancer is a very deadly disease, one of which is leukemia disease or better known as blood cancer. The cancer cell can be detected by taking DNA in laboratory test. This study focused on local alignment of leukemia and non leukemia data resulting from NCBI in the form of DNA sequences by using Smith-Waterman algorithm. SmithWaterman algorithm was invented by TF Smith and MS Waterman in 1981. These algorithms try to find as much as possible similarity of a pair of sequences, by giving a negative value to the unequal base pair (mismatch), and positive values on the same base pair (match). So that will obtain the maximum positive value as the end of the alignment, and the minimum value as the initial alignment. This study will use sequences of leukemia and 3 sequences of non leukemia.

Murine leukemia virus pol gene products: analysis with antisera generated against reverse transcriptase and endonuclease fusion proteins expressed in Escherichia coli

International Nuclear Information System (INIS)

Hu, S.C.; Court, D.L.; Zweig, M.; Levin, J.G.

1986-01-01

The organization of the murine leukemia virus (MuLV) pol gene was investigated by expressing molecular clones containing AKR MuLV reverse transcriptase or endonuclease or both gene segments in Escherichia coli and generating specific antisera against the expressed bacterial proteins. Reaction of these antisera with detergent-disrupted virus precipitated and 80-kilodalton (kDa) protein, the MuLV reverse transcriptase, and a 46-kDa protein which we believe is the viral endonuclease. A third (50-kDa) protein, related to reverse transcriptase, was also precipitated. Bacterial extracts of clones expressing reverse transcriptase and endonuclease sequences competed with the viral 80- and 46-kDa proteins, respectively. These results demonstrate that the antisera are specific for viral reverse transcriptase and endonuclease. Immunoprecipitation of AKR MuLV with antisera prepared against a bacterial protein containing only endonuclease sequences led to the observation that reverse transcriptase and endonuclease can be associated as a complex involving a disulfide bond(s)

Leukemia in Nagasaki atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Brill, A B; Heyssel, R; Itoga, T; Tomonaga, M

1960-08-01

In the 13.5 years following the detonation of the atomic bomb, 95 cases of leukemia have been observed in the Nagasaki survivors. This increase is highly significant statistically. The increased leukemia risk apparently started 1.5 to 2.5 years following radiation exposure, and has lasted through 1958. Acute leukemias of all types and chronic granulocytic leukemia are increased, (with the possible exception of the Schilling type of acute monocytic leukemia). Males in general, and individuals in the younger ages (0 to 09), are apparently most sensitive. The risk of radiation induction of leukemia is related to the size of the dose. The shape of the curve does not differ greatly from a linear model, but is consistent with a variety of hypotheses. The data in the low dose region are too limited to be of significance in evaluating the risk of low doses of radiation. The data suggest that high radiation doses may be associated with a decrease in the latent period to leukemia induction. 43 references, 2 figures, 31 tables.

The Danish National Acute Leukemia Registry

DEFF Research Database (Denmark)

Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

2016-01-01

AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

Science.gov (United States)

2014-08-26

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

The need to accessorize: Molecular roles of HTLV-1 p30 and HTLV-2 p28 accessory proteins in the viral life cycle

Directory of Open Access Journals (Sweden)

Rajaneesh eAnupam

2013-09-01

Full Text Available Extensive studies of HTLV-1 and HTLV-2 over the last three decades have provided detailed knowledge on viral transformation, host-viral interactions and pathogenesis. HTLV-1 is the etiological agent of adult T cell leukemia (ATL and multiple neurodegenerative and inflammatory diseases while HTLV-2 disease association remains elusive, with few infected individuals displaying neurodegenerative diseases similar to HTLV-1. The HTLV group of oncoretroviruses has a genome that encodes structural and enzymatic proteins Gag, Pro and Env, regulatory proteins Tax and Rex, and several accessory proteins from the pX region. Of these proteins, HTLV-1 p30 and HTLV-2 p28 are encoded by the open reading frame (ORF II of the pX region. Like most other accessory proteins, p30 and p28 are dispensable for in vitro viral replication and transformation but are required for efficient viral replication and persistence in vivo. Both p30 and p28 regulate viral gene expression at the post-transcriptional level whereas p30 can also function at the transcriptional level. Recently, several reports have implicated p30 and p28 in multiple cellular processes, which provide novel insight into HTLV spread and survival and ultimately pathogenesis. In this review we summarize and compare what is known about p30 and p28, highlighting their roles in viral replication and viral pathogenesis.

Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

OpenAIRE

Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

2003-01-01

For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

Down syndrome preleukemia and leukemia.

Science.gov (United States)

Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

2015-02-01

Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need. Copyright © 2015 Elsevier Inc. All rights reserved.

X-ray crystal structure of the N-terminal region of Moloney murine leukemia virus integrase and its implications for viral DNA recognition: N-Terminal Region of M-MuLV Integrase

Energy Technology Data Exchange (ETDEWEB)

Guan, Rongjin [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Aiyer, Sriram [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Cote, Marie L. [Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854; Xiao, Rong [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Jiang, Mei [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Acton, Thomas B. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Roth, Monica J. [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Montelione, Gaetano T. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854

2017-02-03

The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain, and the C-terminal domain. The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1–44) and an HHCC zinc-finger NTD (residues 45–105), in two crystal forms are reported. The structures of IN NTR constructs encoding residues 1–105 (NTR1–105) and 8–105 (NTR8–105) were determined at 2.7 and 2.15 Å resolution, respectively and belong to different space groups. While both crystal forms have similar protomer structures, NTR1–105 packs as a dimer and NTR8–105 packs as a tetramer in the asymmetric unit. The structure of the NED consists of three anti-parallel β-strands and an α-helix, similar to the NED of prototype foamy virus (PFV) IN. These three β-strands form an extended β-sheet with another β-strand in the HHCC Zn2+ binding domain, which is a unique structural feature for the M-MuLV IN. The HHCC Zn2+ binding domain structure is similar to that in HIV and PFV INs, with variations within the loop regions. Differences between the PFV and MLV IN NEDs localize at regions identified to interact with the PFV LTR and are compared with established biochemical and virological data for M-MuLV. Proteins 2017; 85:647–656.

Chronic lymphocytic leukemia (CLL)

Science.gov (United States)

... is used for painful and enlarged lymph nodes. Blood transfusions or platelet transfusions may be required if blood ... unexplained fatigue, bruising, excessive sweating, or weight loss. Alternative ... Leukemia - chronic lymphocytic (CLL); Blood cancer - chronic lymphocytic leukemia; Bone marrow cancer - chronic ...

Leukemia in Hiroshima atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Heyssel, R; Brill, A B; Woodbury, L A; Nishimura, Edwin T; Ghose, Tarunendu; Hoshino, Takashi; Yamasaki, Mitsuru

1959-03-01

This report is intended to provide the basic data pertinent to the leukemia experience observed in the survivors of the Hiroshima atomic explosion. Many of the conclusions in this report are tentative. The one clear fact to emerge is that radiation increases the occurrence rate of leukemia and that the magnitude of increase is dependent on dose received. Additional observations can be made, which, while not definitive in themselves, seem to complement each other, and are corroborated by other experiences in radiation biology. From the data a linear relationship between dose and incidence of leukemia is found. The shape of the relation in the lower dose range is not known with certainty. An approximate minimum time for the appearance of leukemia following radiation is 3 years or less. The data suggest that the time of maximum risk of leukemia may be dependent on the dose of radiation received. In this group the mean latent period is found to lie in the interval between 4 and 8 years following exposure. The length of time during which the increased incidence of leukemia persists is not known. The incidence of the acute leukemias and of chronic granulocytic leukemia is increased in the exposed survivors. The chronic granulocytic variety is disproportionately increased in Japanese survivors of the atomic bomb. No effect of radiation on monocytic or chronic lymphatic leukemia incidence is noted. Aplastic anemia, polycythemia vera, and myelofibrosis have been investigated. Myelofibrosis is the only one of this group of diseases in which a suggestive relation to radiation exposure is apparent. The natural history of leukemia following radiation does not seem to differ from that of the spontaneously occurring variety. 17 references, 5 figures, 38 tables.

Analysis of peroxidase-negative acute unclassifiable leukemias by monoclonal antibodies. 1. Acute myelogenous leukemia and acute myelomonocytic leukemia.

Science.gov (United States)

Imamura, N; Tanaka, R; Kajihara, H; Kuramoto, A

1988-11-01

In this study, pretreatment peripheral and/or bone marrow blasts from 12 patients with acute unclassifiable leukemia (AUL) expressing the myeloid-related cell-surface antigen (CD 11) were isolated for further analysis. Despite a lack of myeloperoxidase (MPO) activity, 1 patient's blasts contained cytoplasmic Auer rods. The circulating blasts from another patient expressed MPO while maintaining the same surface phenotype during 20 months of clinical follow-up. In addition, the blasts from 3 cases demonstrated both myelomonocytic and monocyte-specific surface antigens, whereas the remaining 9 cases completely lacked any monocyte-specific antigen detectable by monoclonal antibodies, Mo2, My4 and Leu M3 (CD 14). The first case eventually was diagnosed as acute myelomonocytic leukemia and the second as acute myelogenous leukemia by means of immunophenotypic analysis using flow cytometry (FACS IV). In addition, the presence of MPO protein was identified in the cytoplasm of blast cells from 5 patients with AUL by means of a cytoplasmic immunofluorescence test using a monoclonal antibody (MA1). Our study indicates that non-T, non-B AUL expressing OKM1 (CD 11) antigens include acute leukemias which are unequivocally identifiable as being of either myeloid or myelomonocytic origin. However, further investigations, including immunophenotypic and cytoplasmic analysis, ultrastructural cytochemistry and gene analysis with molecular probes (tests applicable to normal myeloid cells), are necessary in order to determine the actual origin of blasts and to recognize the differentiation stages of the various types of leukemic cells from patients with undifferentiated forms of leukemia.

Association of leukemia with radium groundwater contamination

International Nuclear Information System (INIS)

Lyman, G.H.; Lyman, C.G.; Johnson, W.

1985-01-01

Radiation exposure, including the ingestion of radium, has been causally associated with leukemia in man. Groundwater samples from 27 counties on or near Florida phosphate lands were found to exceed 5 pCi/L total radium in 12.4% of measurements. The incidence of leukemia was greater in those counties with high levels of radium contamination (greater than 10% of the samples contaminated) than in those with low levels of contamination. Rank correlation coefficients of .56 and .45 were observed between the radium contamination level and the incidence of total leukemia and acute myeloid leukemia, respectively. The standardized incidence density ratio for those in high-contamination counties was 1.5 for total leukemia and 2.0 for acute myeloid leukemia. Further investigation is necessary, however, before a causal relationship between groundwater radium content and human leukemia can be established

Roles of HTLV-1 basic Zip Factor (HBZ in Viral Chronicity and Leukemic Transformation. Potential New Therapeutic Approaches to Prevent and Treat HTLV-1-Related Diseases

Directory of Open Access Journals (Sweden)

Jean-Michel Mesnard

2015-12-01

Full Text Available More than thirty years have passed since human T-cell leukemia virus type 1 (HTLV-1 was described as the first retrovirus to be the causative agent of a human cancer, adult T-cell leukemia (ATL, but the precise mechanism behind HTLV-1 pathogenesis still remains elusive. For more than two decades, the transforming ability of HTLV-1 has been exclusively associated to the viral transactivator Tax. Thirteen year ago, we first reported that the minus strand of HTLV-1 encoded for a basic Zip factor factor (HBZ, and since then several teams have underscored the importance of this antisense viral protein for the maintenance of a chronic infection and the proliferation of infected cells. More recently, we as well as others have demonstrated that HBZ has the potential to transform cells both in vitro and in vivo. In this review, we focus on the latest progress in our understanding of HBZ functions in chronicity and cellular transformation. We will discuss the involvement of this paradigm shift of HTLV-1 research on new therapeutic approaches to treat HTLV-1-related human diseases.

42 CFR 81.24 - Guidelines for leukemia.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

Incidence of leukemia, lymphoma and thyroid cancers in children under 15 years old in the vicinity of Marcoule nuclear plant, 1985-95

International Nuclear Information System (INIS)

Bouges, S.; Daures, J.P.; Hebrard, M.

1999-01-01

The aim of this investigation was to report incidence of childhood leukemia, lymphoma and thyroid neoplasms in children under 15 years of age living in the vicinity of the French Marcoule nuclear reprocessing plant. This exhaustive and retrospective survey was carried out between 1985 and 1995 in children aged under 14 at the time of diagnosis and living inside a 35 kilometer zone around the nuclear site. 656 practitioners, 109 medical analysis laboratories and 5 hospitals or cancer institutes were investigated. A panel of experts checked each case. 48 cases of acute leukemia (39 acute lymphoid leukemia and 9 acute myeloid leukemia), 15 cases of lymphoma (8 Hodgkin lymphomas - 53 % - and 7 non hodgkinian lymphomas including 5 Burkitt lymphomas), 1 case of chronic myeloid leukemia and 1 case of papillary thyroid cancer, appeared among the 1,116,442 children-years followed. The total incidences of leukemias and lymphomas were respectively 4.12 and 1.29.10 -5 . Standardised Incidence Ratios, calculated according to Poisson methods and Bayesian inference, with various reference rates did not show any excess of risk: 100.67 (95 % confidence interval 72-131) for leukemia. Children under 5 years old and living in non exposed areas to dominant winds or downstream Rhodanian water drawing presented a 3 or 4 fold decreased risk of leukemia than others (the latter still having an identical risk to that of the general population). This was not true for lymphomas, nor for the other age groups. Over the entire zone, children do not have an increased risk of malignant hematology disease but health monitoring by a systematic collection of cases remains useful around Marcoule. The assumption of aquiferous or air contamination thus still remains questionable: further studies investigating models of contamination are needed to take into account all other nonionizing leukemogenic factors (benzene and viral infection in particular) or correlation studies between health indicators and

An Endogenous Murine Leukemia Viral Genome Contaminant in a Commercial RT-PCR Kit is Amplified Using Standard Primers for XMRV

Directory of Open Access Journals (Sweden)

Miyazawa Takayuki

2010-12-01

Full Text Available Abstract During pilot studies to investigate the presence of viral RNA of xenotropic murine leukemia virus (MLV-related virus (XMRV infection in sera from chronic fatigue syndrome (CFS patients in Japan, a positive band was frequently detected at the expected product size in negative control samples when detecting a partial gag region of XMRV using a one-step RT-PCR kit. We suspected that the kit itself might have been contaminated with small traces of endogenous MLV genome or XMRV and attempted to evaluate the quality of the kit in two independent laboratories. We purchased four one-step RT-PCR kits from Invitrogen, TaKaRa, Promega and QIAGEN in Japan. To amplify the partial gag gene of XMRV or other MLV-related viruses, primer sets (419F and 1154R, and GAG-I-F and GAG-I-R which have been widely used in XMRV studies were employed. The nucleotide sequences of the amplicons were determined and compared with deposited sequences of a polytropic endogenous MLV (PmERV, XMRV and endogenous MLV-related viruses derived from CFS patients. We found that the enzyme mixtures of the one-step RT-PCR kit from Invitrogen were contaminated with RNA derived from PmERV. The nucleotide sequence of a partial gag region of the contaminant amplified by RT-PCR was nearly identical (99.4% identity to a PmERV on chromosome 7 and highly similar (96.9 to 97.6% to recently identified MLV-like viruses derived from CFS patients. We also determined the nucleotide sequence of a partial env region of the contaminant and found that it was almost identical (99.6% to the PmERV. In the investigation of XMRV infection in patients of CFS and prostate cancer, researchers should prudently evaluate the test kits for the presence of endogenous MLV as well as XMRV genomes prior to PCR and RT-PCR tests.

Viral Hepatitis

Science.gov (United States)

... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

Acute childhood leukemia: Nursing care

International Nuclear Information System (INIS)

Zietz, Hallie A

1997-01-01

Modern therapy for childhood acute leukemia has provided a dramatically improved prognosis over that of just 30 years ago. In the early 1960's survival rates for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) were 4% and 3%, respectively. By the 1980's survival rates had risen to 72% for all and 25% to 40% for AML. Today, a diagnosis of all carries an 80% survival rate and as high as a 90% survival rate for some low-risk subtypes. Such high cure rates depend on intense and complex, multimodal therapeutic protocols. Therefore, nursing care of the child with acute leukemia must meet the demands of complicated medical therapies and balance those with the needs of a sick child and their concerned family. An understanding of disease process and principles of medical management guide appropriate and effective nursing interventions. Leukemia is a malignant disorder of the blood and blood- forming organs (bone marrow, lymph nodes and spleen). Most believe that acute leukemia results from a malignant transformation of a single early haematopoietic stem cell that is capable of indefinite self-renewal. These immature cells of blasts do not respond to normal physiologic stimuli for differentiation and gradually become the predominant cell in the bone marrow

Stages of Chronic Myelogenous Leukemia

Science.gov (United States)

... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

Directory of Open Access Journals (Sweden)

Marcia Bellon

2017-10-01

Full Text Available The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein–Barr virus (EBV, Hepatitis B/C/D virus (HBV/HCV/HDV, human herpesvirus 8 (HHV-8, human immunodeficiency virus (HIV, human T-cell leukemia virus type I (HTLV-I, human papillomavirus (HPV, herpes simplex virus-1/2(HSV-1/2, and Varicella–Zoster virus (VZV. Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line

Science.gov (United States)

Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

2016-04-01

First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma.

Science.gov (United States)

Weiser, Keith C; Liu, Bin; Hansen, Gwenn M; Skapura, Darlene; Hentges, Kathryn E; Yarlagadda, Sujatha; Morse Iii, Herbert C; Justice, Monica J

2007-10-01

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFkappaB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision .

Leukemia and radium groundwater contamination

International Nuclear Information System (INIS)

Tracy, B.L.; Letourneau, E.G.

1986-01-01

In the August 2, 1985, issue of JAMMA, Lyman et al claim to have shown an association between leukemia incidence in Florida and radium in groundwater supplies. Although cautious in their conclusions, the authors imply that this excess in leukemia was in fact caused by radiation. The authors believe they have not presented a convincing argument for causation. The radiation doses at these levels of exposure could account for only a tiny fraction of the leukemia excess

Ultrasound and MR Findings of Aleukemic Leukemia Cutis in a Patient with Complete Remission of Acute Lymphoblastic Leukemia: A Case Report

International Nuclear Information System (INIS)

Kim, Min Sung; Jee, Won Hee; Kim, Sun Ki; Lee, So Yeon; Lim, Gye Yeon; Park, Gyeong Sin; Lee, Seok

2010-01-01

Aleukemic leukemia cutis is an extremely rare condition characterized by the infiltration of leukemic cells in skin without blasts in the peripheral blood. Leukemia cutis is considered a grave prognostic sign, thus early diagnosis is important. Leukemia cutis usually occurs in patients with myeloid leukemia. To the best of our knowledge, there has been no report regarding the radiological findings of aleukemic leukemia cutis, which is probably due to the presence of the skin changes in most patients. We report the ultrasound and MR findings of aleukemic leukemia cutis, even without the skin manifestation in patients with a history of complete remission of the acute lymphoblastic leukemia following an allogeneic peripheral blood stem cell transplantation

Ultrasound and MR Findings of Aleukemic Leukemia Cutis in a Patient with Complete Remission of Acute Lymphoblastic Leukemia: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Kim, Min Sung; Jee, Won Hee; Kim, Sun Ki; Lee, So Yeon; Lim, Gye Yeon; Park, Gyeong Sin; Lee, Seok [Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2010-12-15

Aleukemic leukemia cutis is an extremely rare condition characterized by the infiltration of leukemic cells in skin without blasts in the peripheral blood. Leukemia cutis is considered a grave prognostic sign, thus early diagnosis is important. Leukemia cutis usually occurs in patients with myeloid leukemia. To the best of our knowledge, there has been no report regarding the radiological findings of aleukemic leukemia cutis, which is probably due to the presence of the skin changes in most patients. We report the ultrasound and MR findings of aleukemic leukemia cutis, even without the skin manifestation in patients with a history of complete remission of the acute lymphoblastic leukemia following an allogeneic peripheral blood stem cell transplantation

Acute leukemias of ambiguous lineage.

Science.gov (United States)

Béné, Marie C; Porwit, Anna

2012-02-01

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called "leukemias of ambiguous lineage." The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome 11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most from rapid allogeneic hematopoietic stem cell transplantation.

Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

OpenAIRE

Fischinger, P J; Thiel, H J; Blevins, C S; Dunlop, N M

1981-01-01

We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow t...

Residential mobility and childhood leukemia.

Science.gov (United States)

Amoon, A T; Oksuzyan, S; Crespi, C M; Arah, O A; Cockburn, M; Vergara, X; Kheifets, L

2018-07-01

Studies of environmental exposures and childhood leukemia studies do not usually account for residential mobility. Yet, in addition to being a potential risk factor, mobility can induce selection bias, confounding, or measurement error in such studies. Using data collected for California Powerline Study (CAPS), we attempt to disentangle the effect of mobility. We analyzed data from a population-based case-control study of childhood leukemia using cases who were born in California and diagnosed between 1988 and 2008 and birth certificate controls. We used stratified logistic regression, case-only analysis, and propensity-score adjustments to assess predictors of residential mobility between birth and diagnosis, and account for potential confounding due to residential mobility. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status. Odds ratios for leukemia among non-movers living mobility, including dwelling type, increased odds ratios for leukemia to 2.61 (95% CI: 1.76-3.86) for living mobility of childhood leukemia cases varied by several sociodemographic characteristics, but not by the distance to the nearest power line or calculated magnetic fields. Mobility appears to be an unlikely explanation for the associations observed between power lines exposure and childhood leukemia. Copyright © 2018 Elsevier Inc. All rights reserved.

Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia

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Matsuo, Tatsuki; Tomonaga, Masao; Bennett, J.M. and others

1988-06-01

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85 % agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2 %. The present study suggest that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia

International Nuclear Information System (INIS)

Matsuo, Tatsuki; Tomonaga, Masao; Bennett, J.M.

1988-01-01

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85 % agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2 %. The present study suggest that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure. (author)

Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias

International Nuclear Information System (INIS)

Philip, P.; Pedersen-Bjergaard, J.

1988-01-01

From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease

Infection and childhood leukemia: review of evidence

Directory of Open Access Journals (Sweden)

Raquel da Rocha Paiva Maia

2013-12-01

Full Text Available OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection, and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

Thrombocytopenia in leukemia: Pathogenesis and prognosis.

Science.gov (United States)

Shahrabi, Saeid; Behzad, Masumeh Maleki; Jaseb, Kaveh; Saki, Najmaldin

2018-02-20

Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways

Directory of Open Access Journals (Sweden)

Robert eCurrer

2012-11-01

Full Text Available Human T cell lymphotropic virus type 1 (HTLV-1 has been identified as the causative agent of adult T cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The virus infects between 15 and 20 million people worldwide of which approximately 2 to 5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications of Tax and sub-cellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis.

HTLV Tax: A Fascinating Multifunctional Co-Regulator of Viral and Cellular Pathways

Science.gov (United States)

Currer, Robert; Van Duyne, Rachel; Jaworski, Elizabeth; Guendel, Irene; Sampey, Gavin; Das, Ravi; Narayanan, Aarthi; Kashanchi, Fatah

2012-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications (PTMs) of Tax and subcellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis. PMID:23226145

Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

International Nuclear Information System (INIS)

Wang, Jiying; Rao, Qing; Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang

2009-01-01

Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

Energy Technology Data Exchange (ETDEWEB)

Wang, Jiying [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Rao, Qing, E-mail: raoqing@gmail.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)

2009-09-04

Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

Overexpression of feline tripartite motif-containing 25 interferes with the late stage of feline leukemia virus replication.

Science.gov (United States)

Koba, Ryota; Oguma, Keisuke; Sentsui, Hiroshi

2015-06-02

Tripartite motif-containing 25 (TRIM25) regulates various cellular processes through E3 ubiquitin ligase activity. Previous studies have revealed that the expression of TRIM25 is induced by type I interferon and that TRIM25 is involved in the host cellular innate immune response against retroviral infection. Although retroviral infection is prevalent in domestic cats, the roles of feline TRIM25 in the immune response against these viral infections are poorly understood. Because feline TRIM25 is expected to modulate the infection of feline leukemia virus (FeLV), we investigated its effects on early- and late-stage FeLV replication. This study revealed that ectopic expression of feline TRIM25 in HEK293T cells reduced viral protein levels leading to the inhibition of FeLV release. Our findings show that feline TRIM25 has a potent antiviral activity and implicate an antiviral mechanism whereby feline TRIM25 interferes with late-stage FeLV replication. Copyright © 2015 Elsevier B.V. All rights reserved.

Appearance and Disappearance of Chronic Myeloid Leukemia (CML) in Patient with Chronic Lymphocytic Leukemia (CLL)

OpenAIRE

Payandeh, Mehrdad; Sadeghi, Edris; Khodarahmi, Reza; Sadeghi, Masoud

2014-01-01

Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common leukemias of the elderly (>43 year). However, the sequential occurrence of CML followed by CLL in the same patient is extremely rare. In our report, a 52-year-old female was diagnosed with CLL (type of bone marrow (BM) infiltration was nodular and interstitial) and was treated with chlorambucil. 64 months after the diagnosis of CLL, she developed CML. She was treated with imatinib (400mg/day). After a fe...

Risk Groups for Childhood Acute Lymphoblastic Leukemia

Science.gov (United States)

... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

Treatment Options for Childhood Acute Lymphoblastic Leukemia

Science.gov (United States)

... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

General Information about Childhood Acute Lymphoblastic Leukemia

Science.gov (United States)

... cells in the blood at the time of diagnosis. Whether the leukemia cells began from B lymphocytes or T lymphocytes. ... How long it is between the time of diagnosis and when the leukemia comes back. Whether the leukemia comes back in ...

Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro

International Nuclear Information System (INIS)

Kawasaki, E.S.; Clark, S.S.; Coyne, M.Y.; Smith, S.D.; Champlin, R.; Witte, O.N.; McCormick, F.P.

1988-01-01

The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, the authors have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome

Acute myeloid leukemia (AML) - children

Science.gov (United States)

Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

Molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

Energy Technology Data Exchange (ETDEWEB)

Meruelo, D; Rossomando, A

1986-01-01

The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1.

Human T cell lymphotropic virus type I genomic expression and impact on intracellular signaling pathways during neurodegenerative disease and leukemia.

Science.gov (United States)

Yao, J; Wigdahl, B

2000-01-01

HTLV-I has been identified as the etiologic agent of neoplasia within the human peripheral blood T lymphocyte population, and a progressive neurologic disorder based primarily within the central nervous system. We have examined the role of HTLV-I in these two distinctly different clinical syndromes by examining the life cycle of the virus, with emphasis on the regulation of viral gene expression within relevant target cell populations. In particular, we have examined the impact of specific viral gene products, particularly Tax, on cellular metabolic function. Tax is a highly promiscuous and pleiotropic viral oncoprotein, and is the most important factor contributing to the initial stages of viral-mediated transformation of T cells after HTLV-I infection. Tax, which weakly binds to Tax response element 1 (TRE-1) in the viral long terminal repeat (LTR), can dramatically trans-activate viral gene expression by interacting with cellular transcription factors, such as activated transcription factors and cyclic AMP response element binding proteins (ATF/CREB), CREB binding protein (CBP/p300), and factors involved with the basic transcription apparatus. At the same time, Tax alters cellular gene expression by directly or indirectly interacting with a variety of cellular transcription factors, cell cycle control elements, and cellular signal transduction molecules ultimately resulting in dysregulated cell proliferation. The mechanisms associated with HTLV-I infection, leading to tropical spastic paraparesis (TSP) are not as clearly resolved. Possible explanations of viral-induced neurologic disease range from central nervous system (CNS) damage caused by direct viral invasion of the CNS to bystander CNS damage caused by the immune response to HTLV-I infection. It is interesting to note that it is very rare for an HTLV-I infected individual to develop both adult T cell leukemia (ATL) and TSP in his/her life time, suggesting that the mechanisms governing development of these

Distribution of onset of leukemia among atomic bomb survivors in the leukemia registry by dose, Hiroshima and Nagasaki, 1946-75

International Nuclear Information System (INIS)

Ishimaru, Toranosuke; Ichimaru, Michito; Mikami, Motoko; Yamada, Yasuaki; Tomonaga, Yuu.

1982-03-01

The data from the RERF Leukemia Registry for the years 1946-75 were used to determine the distribution of onset of acute leukemia and chronic granulocytic leukemia among atomic bomb survivors in relation to city, dose, and age at the time of the bomb (ATB). A total of 509 confirmed leukemia cases (297 in Hiroshima and 212 in Nagasaki) have occurred among A-bomb survivors in the open populations of these cities in these years. Analysis revealed that the onset of both acute leukemia and chronic granulocytic leukemia tends to shift to earlier years with increasing dose in Hiroshima, but in Nagasaki, although the onset of both types of leukemia was earlier in the high dose group than in the low dose or control groups, the latter two groups did not differ. The distribution of onset of acute leukemia in the three dose groups also depended upon age ATB. While the distribution of onset of acute leukemia among those survivors whose age ATB was less than 30 differed significantly in the three dose classes, this tendency was not observed among those individuals whose age ATB was 30 years or more. For chronic granulocytic leukemia, the onset was shifted to earlier years in the high dose group than in the control group regardless of age ATB in Hiroshima. These findings support the pattern of leukemogenesis observed in A-bomb survivors in the Life Span Study sample, a fixed cohort, in relation to city, dose, age ATB, and years after exposure. (author)

AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

Science.gov (United States)

2018-03-12

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Radiotherapy for leukemia in children, (1)

International Nuclear Information System (INIS)

Miyazaki, Toru; Konishi, Kiyosaburo; Sato, Noriko; Fujiwara, Fumihiro

1983-01-01

Following the development of effective chemotherapy for producing remissions of acute lymphocytic leukemia (ALL), a new phenomenon has emerged in this disease--central nervous system (CNS) leukemia. CNS leukemia has become an increasingly frequent obstacle to prolongation of initial complete remission. Prophylactic irradiation of the CNS concomitant with intrathecal administration of methotrexate (IT-MTX) has proved to be effective in the reduction of CNS involvement. The purpose of this paper is to describe the results of irradiation for prevention of CNS leukemia and to discuss their implications. The patients consisted of 32 children with acute leukemia, admitted to MAIZURU National Hospital from 1966 to 1980; 22 patients of them had ALL, the others ANLL (acute non-lymphocytic leukemia). Preventive CNS therapy was started in 1974, (group A), but there was no prevention before 1974 (group B). 1. In group B, six patients was treated by therapeutic cranial irradiation, but all cases resulted in death. 2. In group A, seven patients was treated by prophylactic cranial irradiation combined with IT-MTX, and all of them have been alive without CNS relapse for 2 to 4 2/3 years after therapy. 3. In group A, none of 7 patients (0 %) relapsed CNS leukemia initially as compared to 7 (50 %) of 14 in group B, thus preventive efficacy was clear. 4. There were no severe complications attributable to the radiotherapy, with or without IT-MTX. (author)

Viral Determinants of FeLV Infection and Pathogenesis: Lessons Learned from Analysis of a Natural Cohort

Directory of Open Access Journals (Sweden)

Laura S. Levy

2011-09-01

Full Text Available Detailed analysis has been performed over many years of a geographic and temporal cohort of cats naturally infected with feline leukemia virus (FeLV. Molecular analysis of FeLV present in the diseased tissues and application of those viruses to experimental systems has revealed unique isolates with distinctive disease potential, previously uncharacterized virus-receptor interactions, information about the role of recombinant viruses in disease induction, and novel viral and cellular oncogenes implicated in pathogenesis, among other findings. The studies have contributed to an understanding of the selective forces that lead to predominance of distinctive FeLV isolates and disease outcomes in a natural population.

Epidemiological assessment of leukemia in Kazakhstan, 2003- 2012.

Science.gov (United States)

Igissinov, Nurbek; Kulmirzayeva, Dariyana; Moore, Malcolm A; Igissinov, Saginbek; Baidosova, Gulnara; Akpolatova, Gulnur; Bukeyeva, Zhanar; Omralina, Yelvira

2014-01-01

Cancer is a major health problem facing the entire world, and Kazakhstan is not the exception. The aim of this study was to present an epidemiological assessment of leukemia in the population of Kazakhstan during 2003-2012. This descriptive and retrospective study was based on data obtained from all oncological organizations of the whole country. Age standardized incidence rates per 100,000 population for leukemia were calculated. Totally, 6,741 new cases of leukemia were registered in Kazakhstan during the 10 year period. The mean age of patients with leukemia was 48.5. The ASRs for leukemia among men and women were 5.3 and 3.6, respectively (pKazakhstan, especially in the north of the country. The incidence of leukemia was significantly higher in males and increased with age. Determining and controlling important risk factors of leukemia may lead to decrease in its burden.

Leukemia and lymphoma in atomic bomb survivors

International Nuclear Information System (INIS)

Finch, S.C.

1984-01-01

Leukemia has been observed to increase with increasing radiation dose in the A-bomb survivors of Hiroshima and Nagasaki. The first radiation-related cases occurred 3 to 5 years following exposure. The peak incidence years were about 7 to 8 years following exposure and the leukemogenic effect has decreased since that time, but it may last for 40 years or longer in the most heavily exposed persons. A bimodal susceptibility pattern was observed, with peaks following exposure during childhood and after age 50. Latent periods for the development of acute leukemia were shortest in the younger exposed persons. Both acute and chronic forms of leukemia occurred in exposed persons at younger ages in life than normally is expected. The most common types of radiation-induced leukemia were acute and chronic granulocytic in adults and children, and acute lymphocytic in children. The highest radiation-related leukemia risk was for chronic granulocytic leukemia following childhood exposure

[Molecular characterization of atypical chronic myeloid leukemia and chronic neutrophilic leukemia].

Science.gov (United States)

Senín, Alicia; Arenillas, Leonor; Martínez-Avilés, Luz; Fernández-Rodríguez, Concepción; Bellosillo, Beatriz; Florensa, Lourdes; Besses, Carles; Álvarez-Larrán, Alberto

2015-06-08

Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) display similar clinical and hematological characteristics. The objective of the present study was to determine the mutational status of SETBP1 and CSF3R in these diseases. The mutational status of SETBP1 and CSF3R was studied in 7 patients with aCML (n = 3), CNL (n = 1) and unclassifiable myeloproliferative neoplasms (MPN-u) (n = 3). Additionally, mutations in ASXL1, SRSF2, IDH1/2, DNMT3A, and RUNX1 were also analyzed. SETBP1 mutations (G870S and G872R) were detected in 2 patients with MPN-u, and one of them also presented mutations in SRSF2 (P95H) and ASXL1 (E635fs). The CNL case showed mutations in CSFR3 (T618I), SETBP1 (G870S) and SRSF2 (P95H). No patient classified as aCML had mutations in SETBP1 or CSF3R. One of the patients with mutations evolved to acute myeloid leukemia, while the other 2 had disease progression without transformation to overt leukemia. The knowledge of the molecular alterations involved in these rare diseases is useful in the diagnosis and may have an impact on both prognosis and therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Monoclonal antibodies reactive with hairy cell leukemia

NARCIS (Netherlands)

Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

Trisomy/tetrasomy 13 in seven cases of acute leukemia.

Science.gov (United States)

Sreekantaiah, C; Baer, M R; Morgan, S; Isaacs, J D; Miller, K B; Sandberg, A A

1990-11-01

We report the clinical presentation and the morphologic, histochemical, and immunophenotypic characteristics of seven patients with acute leukemia who had trisomy/tetrasomy 13 as the sole cytogenetic abnormality in their leukemia. Five patients had trisomy 13 at diagnosis of acute leukemia. All five of these patients had undifferentiated leukemias. The sixth patient, who had French-American-British (FAB) type M2 acute nonlymphocytic leukemia (ANLL), and the seventh patient with biphenotypic acute leukemia developed the trisomic clone as a new abnormality late in the course of their disease. A review of the literature revealed 28 previously reported hematologic malignancies with trisomy 13 or tetrasomy 13q as a solitary cytogenetic abnormality. Trisomy 13 appears to represent another rare but nonrandom cytogenetic abnormality in acute leukemia. In our series trisomy 13 is largely associated with acute leukemia with little myeloid or lymphoid differentiation.

Central nervous system in leukemia

Energy Technology Data Exchange (ETDEWEB)

Phair, J P; Anderson, R E; Namiki, Hideo

1964-03-12

The present report summarizes the pertinent clinical and pathologic findings in 165 cases of leukemia in atomic bomb exposed victims autopsied during the period 1949 to 1962 at ABCC in Hiroshima and Nagasaki, Japan. Significant parenchymal hemorrhage occurred most often in acute myelogenous leukemia and was markedly increased in patients dying with high terminal white blood cell counts. Possible mechanisms involved in the pathogenesis of cerebral hemorrhage in leukemia are discussed. Subarachnoid hemorrhage and subdural hematoma were not related to leukocytosis but appeared to be influenced by marked thrombocytopenia. Leukemic infiltrates of a diffuse nature involving the meninges were paradoxically increased in patients receiving adequate chemotherapy. Meningeal tumors did not show this peculiar relationship to therapy and were not found in association with lymphatic leukemia. Infections involving the central nervous system were confined to patients receiving chemotherapy including steroids. 39 references, 3 figures, 4 tables.

Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

International Nuclear Information System (INIS)

Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

2011-01-01

Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

Treatment Option Overview (Chronic Myelogenous Leukemia)

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... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

General Information about Chronic Myelogenous Leukemia

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... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia.

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Pleyer, Christopher; Wiestner, Adrian; Sun, Clare

2018-05-15

Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib. While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents. This review discusses the impact of ibrutinib and idelalisib on the immune system, including infectious and auto-immune complications as well as their specific effects on the B-cell, T-cell, and myeloid compartment.

Perspectives on the causes of childhood leukemia.

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Wiemels, Joseph

2012-04-05

Acute leukemia is the most common cancer in children but the causes of the disease in the majority of cases are not known. About 80% are precursor-B cell in origin (CD19+, CD10+), and this immunophenotype has increased in incidence over the past several decades in the Western world. Part of this increase may be due to the introduction of new chemical exposures into the child's environment including parental smoking, pesticides, traffic fumes, paint and household chemicals. However, much of the increase in leukemia rates is likely linked to altered patterns of infection during early childhood development, mirroring causal pathways responsible for a similarly increased incidence of other childhood-diagnosed immune-related illnesses including allergy, asthma, and type 1 diabetes. Factors linked to childhood leukemia that are likely surrogates for immune stimulation include exposure to childcare settings, parity status and birth order, vaccination history, and population mixing. In case-control studies, acute lymphoblastic leukemia (ALL) is consistently inversely associated with greater exposure to infections, via daycare and later birth order. New evidence suggests also that children who contract leukemia may harbor a congenital defect in immune responder status, as indicated by lower levels of the immunosuppressive cytokine IL-10 at birth in children who grow up to contract leukemia, as well as higher need for clinical care for infections within the first year of life despite having lower levels of exposure to infections. One manifestation of this phenomenon may be leukemia clusters which tend to appear as a leukemia "outbreak" among populations with low herd immunity to a new infection. Critical answers to the etiology of childhood leukemia will require incorporating new tools into traditional epidemiologic approaches - including the classification of leukemia at a molecular scale, better exposure assessments at all points in a child's life, a comprehensive

Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

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... associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description PDGFRB -associated chronic eosinophilic leukemia is a type of cancer of blood-forming ...

Leukemia -- Eosinophilic

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... social workers, and patient advocates. Cancer.Net Guide Leukemia - Eosinophilic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

A molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

International Nuclear Information System (INIS)

Meruelo, D.; Rossomando, A.

1986-01-01

The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1. (author)

Extramedullary leukemia in children presenting with proptosis

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Naik Milind

2009-01-01

Full Text Available Abstract Background We highlight the orbital manifestations of acute myeloid leukemia and the role of peripheral blood smear in the diagnosis of these cases. A total of 12 patients who presented with proptosis and were subsequently diagnosed to have acute myeloid leukemia based on incision biopsy or peripheral blood smear were included in the study. Results A retrospective review of all cases of acute myeloid leukemia presenting to the Orbital clinic was performed. The age at presentation, gender, presenting features, duration of symptoms and fundus features were noted. In addition the temporal relationship of the orbital disease to the diagnosis of leukemia, laterality, location of the orbital mass, imaging features and the diagnostic tools used to diagnose leukemia were noted. The median age at presentation was 6 years. The male: female ratio was 0.7:1. None of these patients had been diagnosed earlier as having acute myeloid leukemia. The presenting features included proptosis in all patients, orbital mass in 5 (41.7%, visual symptoms in 2 (16.7% and subconjunctival hemorrhage in one patient (8.3%. A diagnosis of acute myeloid leukemia was established by incision biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing and bone marrow biopsy in 2 patients which revealed the presence of systemic involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8 patients presenting with ocular manifestations, diagnosis was established by peripheral blood smear examination alone which revealed a diagnosis of acute myeloid leukemia. Conclusion A peripheral blood smear should be performed in all cases of sudden onset proptosis or an orbital mass in children and young adults along with an orbital biopsy. It can always be complemented with a bone marrow biopsy especially in cases of aleukemic leukemia or when the blood smear is inconclusive.

Pharmacogenetics in Acute Lymphoblastic Leukemia

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Cheok, Meyling H.; Pottier, Nicolas; Kager, Leo

2009-01-01

Progress in the treatment of acute leukemia in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute lymphoblastic leukemia. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm. PMID:19100367

Appearance and Disappearance of Chronic Myeloid Leukemia (CML) in Patient with Chronic Lymphocytic Leukemia (CLL).

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Payandeh, Mehrdad; Sadeghi, Edris; Khodarahmi, Reza; Sadeghi, Masoud

2014-10-01

Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common leukemias of the elderly (>43 year). However, the sequential occurrence of CML followed by CLL in the same patient is extremely rare. In our report, a 52-year-old female was diagnosed with CLL (type of bone marrow (BM) infiltration was nodular and interstitial) and was treated with chlorambucil. 64 months after the diagnosis of CLL, she developed CML. She was treated with imatinib (400mg/day). After a few months, signs of CML were disappeared and CLL became dominant. This is first reported case.

Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection

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Millet, Jean Kaoru; Whittaker, Gary R.

2016-01-01

Viral pseudotyped particles (pp) are enveloped virus particles, typically derived from retroviruses or rhabdoviruses, that harbor heterologous envelope glycoproteins on their surface and a genome lacking essential genes. These synthetic viral particles are safer surrogates of native viruses and acquire the tropism and host entry pathway characteristics governed by the heterologous envelope glycoprotein used. They have proven to be very useful tools used in research with many applications, such as enabling the study of entry pathways of enveloped viruses and to generate effective gene-delivery vectors. The basis for their generation lies in the capacity of some viruses, such as murine leukemia virus (MLV), to incorporate envelope glycoproteins of other viruses into a pseudotyped virus particle. These can be engineered to contain reporter genes such as luciferase, enabling quantification of virus entry events upon pseudotyped particle infection with susceptible cells. Here, we detail a protocol enabling generation of MLV-based pseudotyped particles, using the Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) as an example of a heterologous envelope glycoprotein to be incorporated. We also describe how these particles are used to infect susceptible cells and to perform a quantitative infectivity readout by a luciferase assay. PMID:28018942

Study of ultrasonic imagine of spleen in patients with leukemia

International Nuclear Information System (INIS)

Zheng Hui; Zhou Chunyan; Jiang Ju; Luo Liying; Huang Yanhong

2011-01-01

To investigate spleen ultrasonic imagine in patients with leukemia and to provide basis information for preventing and treat disease,the spleens imaging of 158 patients with leukemia were detected by B mode ultrasonicgraphy and the data of clinical medical examination were analyzed.The results showed that the spleens' ultrasonic imagine of patients with leukemia were not related to the degree of anemia.The ultrasonic imagines of spleen in patients with chronic leukemia were different to the other kinds of leukemia.The ultrasonic imagine of spleens in leukemia patients are related to types and development of leukemia.The B-ultrasound screening should be used to help clinical diagnosis and treatment of patients with leukemia. (authors)

CD154 costimulated ovine primary B cells, a cell culture system that supports productive infection by bovine leukemia virus.

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Van den Broeke, A; Cleuter, Y; Beskorwayne, T; Kerkhofs, P; Szynal, M; Bagnis, C; Burny, A; Griebel, P

2001-02-01

Bovine leukemia virus (BLV) is closely associated with the development of B-cell leukemia and lymphoma in cattle. BLV infection has also been studied extensively in an in vivo ovine model that provides a unique system for studying B-cell leukemogenesis. There is no evidence that BLV can directly infect ovine B cells in vitro, and there are no direct data regarding the oncogenic potential of the viral Tax transactivator in B cells. Therefore, we developed ovine B-cell culture systems to study the interaction between BLV and its natural target, the B cell. In this study, we used murine CD154 (CD40 ligand) and gamma-chain-common cytokines to support the growth of B cells isolated from ovine lymphoid tissues. Integrated provirus, extrachromosomal forms, and viral transcripts were detected in BLV-exposed populations of immature, rapidly dividing surface immunoglobulin M-positive B cells from sheep ileal Peyer's patches and also in activated mature B cells isolated from blood. Conclusive evidence of direct B-cell infection by BLV was obtained through the use of cloned B cells derived from sheep jejunal Peyer's patches. Finally, inoculation of sheep with BLV-infected cultures proved that infectious virus was shed from in vitro-infected B cells. Collectively, these data confirm that a variety of ovine B-cell populations can support productive infection by BLV. The development of ovine B-cell cultures permissive for BLV infection provides a controlled system for investigating B-cell leukemogenic processes and the pathogenesis of BLV infection.

Pathogenesis and treatment of leukemia: an Asian perspective.

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Kwong, Yok-Lam

2012-03-01

Leukemias occur worldwide, but there are important geographic differences in incidences. Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.

Acute leukemia in early childhood

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M. Emerenciano

2007-06-01

Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress) on the course of progressive feline leukemia virus infection.

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Boesch, Andrea; Cattori, Valentino; Riond, Barbara; Willi, Barbara; Meli, Marina L; Rentsch, Katharina M; Hosie, Margaret J; Hofmann-Lehmann, Regina; Lutz, Hans

2015-02-25

Cats persistently infected with the gammaretrovirus feline leukemia virus (FeLV) are at risk to die within months to years from FeLV-associated disease, such as immunosuppression, anemia or lymphoma/leukemia. The integrase inhibitor raltegravir has been demonstrated to reduce FeLV replication in vitro. The aim of the present study was to investigate raltegravir in vivo for its safety and efficacy to suppress FeLV replication. The safety was tested in three naïve specified pathogen-free (SPF) cats during a 15 weeks treatment period (initially 20mg then 40mg orally b.i.d.). No adverse effects were noted. The efficacy was tested in seven persistently FeLV-infected SPF cats attained from 18 cats experimentally exposed to FeLV-A/Glasgow-1. The seven cats were treated during nine weeks (40mg then 80mg b.i.d.). Raltegravir was well tolerated even at the higher dose. A significant decrease in plasma viral RNA loads (∼5×) was found; however, after treatment termination a rebound effect was observed. Only one cat developed anti-FeLV antibodies and viral RNA loads remained decreased after treatment termination. Of note, one of the untreated FeLV-A infected cats developed fatal FeLV-C associated anemia within 5 weeks of FeLV-A infection. Moreover, progressive FeLV infection was associated with significantly lower enFeLV loads prior to infection supporting that FeLV susceptibility may be related to the genetic background of the cat. Overall, our data demonstrate the ability of raltegravir to reduce viral replication also in vivo. However, no complete control of viremia was achieved. Further investigations are needed to find an optimized treatment against FeLV. (250 words). Copyright © 2014 Elsevier B.V. All rights reserved.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

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Anne M. Dickinson

2017-06-01

Full Text Available The success of hematopoietic stem cell transplantation (HSCT lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL, caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

Sequences responsible for the distinctive hemolytic potentials of Friend and Moloney murine leukemia viruses are dispersed but confined to the psi-gag-PR region.

OpenAIRE

Richardson, J; Corbin, A; Pozo, F; Orsoni, S; Sitbon, M

1993-01-01

Friend and Moloney murine leukemia viruses (F- and M-MuLV) induce distinct diseases in hematopoietic tissues following inoculation of newborn mice of susceptible strains. F-MuLV induces erythroleukemia preceded by severe early hemolytic anemia; M-MuLV induces thymomas and only very mild hemolysis. The major viral determinant of severe early hemolytic anemia residues in the env gene, but sequences located outside this gene can modulate this effect. By means of genetic chimeras of F- and M-MuLV...

[Occurrence of associated tumours in chronic lymphocytic leukemia].

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Szerafin, László; Jakó, János; Varju, Lóránt

2016-10-01

Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

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2018-02-22

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses integrase: critical residues for concerted integration and multimerization

International Nuclear Information System (INIS)

Moreau, Karen; Faure, Claudine; Violot, Sebastien; Gouet, Patrice; Verdier, Gerard; Ronfort, Corinne

2004-01-01

During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the cell DNA by the viral integrase (IN) enzyme. The central core domain of IN contains the catalytic site of the enzyme and is involved in binding viral ends and cell DNA as well as dimerization. We previously performed single amino acid substitutions in the core domain of an Avian Leukemia and Sarcoma Virus (ALSV) IN [Arch. Virol. 147 (2002) 1761]. Here, we modeled the resulting IN mutants and analyzed the ability of these mutants to mediate concerted DNA integration in an in vitro assay, and to form dimers by protein-protein cross-linking and size exclusion chromatography. The N197C mutation resulted in the inability of the mutant to perform concerted integration that was concomitant with a loss of IN dimerization. Surprisingly, mutations Q102G and A106V at the dimer interface resulted in mutants with higher efficiencies than the wild-type IN in performing two-ended concerted integration of viral DNA ends. The G139D and A195V mutants had a trend to perform one-ended DNA integration of viral ends instead of two-ended integration. More drastically, the I88L and L135G mutants preferentially mediated nonconcerted DNA integration although the proteins form dimers. Therefore, these mutations may alter the formation of IN complexes of higher molecular size than a dimer that would be required for concerted integration. This study points to the important role of core domain residues in the concerted integration of viral DNA ends as well as in the oligomerization of the enzyme

Leukemia risk following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Curtis, R.E.; Boice, J.D. Jr.; Stovall, M.; Flannery, J.T.; Moloney, W.C.

1989-01-01

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

Radiation in the treatment of meningeal leukemia

International Nuclear Information System (INIS)

Jenkin, R.D.

1979-01-01

At the present time, a successful regimen for the eradication of occult meningeal leukemia is the combination of cranial radiotherapy in a dose of 1800 rads in 10 fractions in 12 to 14 days with six doses of intrathecal methotrexate. This regimen, when given with prednisone and vincristine can be expected to give a relapse rate for isolated meningeal leukemia of approximately 5% during the first 2 years of follow-up. A modification of this regimen utilizing craniospinal radiation with prior and concurrent intrathecal methotrexate is given for the treatment of overt meningeal leukemia at diagnosis or for an isolated first relapse with meningeal leukemia. Radiation technique and morbidity are discussed

Pharyngitis - viral

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... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...

Cytogenetic basis of acute myeloid leukemia.

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Ford, J H; Pittman, S M; Singh, S; Wass, E J; Vincent, P C; Gunz, F W

1975-10-01

The chromosomes of 12 adult patients with acute leukemia were analyzed by conventional means and by Giemsa and centromeric banding techniques. Acute myeloblastic leukemia was diagnosed in 7, acute myelomonocytic leukemia in 2, and acute undifferentiated leukemia in 3. Bone marrow was aspirated from patients when in relapse or remission, and both euploid and aneuploid cells were examined. All patients showed trisomy no. 9 and many showed additional numerical or structural changes in some or all their cells. These changes included monosomy no. 21 and/or monosomy no. 8. The proportion of trisomy no. 9 cells was 30-50% in patients in full remission and up to 100% in patients in relapse; thus trisomy no. 9 might be an important marker of leukemic cells. A mechanism was proposed to explain the induction and selection of the trisomy no. 9 karotype.

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

Science.gov (United States)

Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

2017-02-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Cranial computerized tomography in children suffering from acute leukemia

International Nuclear Information System (INIS)

Metz, O.

1981-01-01

Cranial computerized (axial) tomography permits a more complete neurologic supervision of children with acute leukemia and a better knowledge of the frequency and varieties of cerebral complications in leukemia. Endocranial complications in acute leukemia are essentially infiltrative, hemorrhagic, infectious or iatrogenic. Cranial computerized tomography can demonstrate cerebral changes in meningeal leukemia, hemorrhages, calcifications, brain atrophy or leukencephalopathy. The preliminary results of cranial computerized tomography in childhood leukemia suggest that the iatrogenic main lesion of the brain due to combined radiation-chemotherapy is atrophy whereas that of the intrathecal cytostatic therapy is demyelination. Accurate diagnostics and control of possible cerebral complications in therapy of leukemia is essentially for appropriate therapeutic management. For that cranial computerized tomography is the best method to a effective supervision of the brain. (author)

Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Michael Schmitt

2007-01-01

Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

Viral Meningitis

Science.gov (United States)

... better from treatment such as an antiviral medicine. Antibiotics do not help viral infections, so they are not useful in the treatment of viral meningitis. However, antibiotics do fight bacteria, so they are very important ...

Leukemia in Hiroshima atomic bomb survivors from 1946 to 1975

International Nuclear Information System (INIS)

Ohkita, Takeshi

1976-01-01

In five recent years, 134 deaths from leukemia among Hiroshima citizen were recorded. Of these, 23 cases (17 acute and 6 chronic types) were atomic bomb survivors exposed within 2,000 m of the hypocenter. Fifteen of them (65%) were over 60 years of age. The frequency of chronic lymphocytic leukemia was still low. Although the risk of leukemia was greatly reduced after 1961, and the frequency of chronic granulocytic leukemia (one of the most characteristic type of Hiroshima atomic bomb-induced leukemia) was also decreased, the death rate from leukemia among survivors exposed within 2,000 m or 1,500 m from the hypocenter was about 3 to 4 times higher than the mean death rate in all Japan. Therefore, careful and long-range follow-up surveillance should be continued. A brief review was also made of relevant studies such as the influence of environmental and host factors in the epidemiology of leukemia, the incidence of leukemia in children exposed in utero, and leukemia in offspring of atomic bomb survivors. (Evans, J.)

Secondary acute leukemia - review of 15 cases

Energy Technology Data Exchange (ETDEWEB)

Venugopal, P; Rajni, A; Gopal, R; Saikia, T; Kurkure, P A; Nair, C N; Advani, S H

1988-12-01

Acute leukemia is a rare complication of long-term chemotherapy, immunosuppressive therapy and radiotherapy. With improved survival in cancer patients resulting from modern methods of investigations and treatment, more case of secondary leukemia have come to light. In this review, fifteen cases of secondary leukemia, its prognostic implications and methods to reduce the risk of its development are emphasised. Relevant literature is also reviewed. (author). 3 tabs., 24 refs.

Cattle with the BoLA class II DRB3*0902 allele have significantly lower bovine leukemia proviral loads.

Science.gov (United States)

Hayashi, Takumi; Mekata, Hirohisa; Sekiguchi, Satoshi; Kirino, Yumi; Mitoma, Shuya; Honkawa, Kazuyuki; Horii, Yoichiro; Norimine, Junzo

2017-09-12

The bovine MHC (BoLA) class II DRB3 alleles are associated with polyclonal expansion of lymphocytes caused by bovine leukemia virus (BLV) infection in cattle. To examine whether the DRB3*0902 allele, one of the resistance-associated alleles, is associated with the proviral load, we measured BLV proviral load of BLV-infected cattle and clarified their DRB3 alleles. Fifty-seven animals with DRB3*0902 were identified out of 835 BLV-infected cattle and had significantly lower proviral load (Pclass II DRA/DRB3*0902 molecule plays an important immunological role in suppressing viral replication, resulting in resistance to the disease progression.

Childhood Leukemia--A Look at the Past, the Present and the Future.

Science.gov (United States)

Findeisen, Regina; Barber, William H.

1997-01-01

Provides an overview of childhood leukemia. The causes, the survival period, different types (acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and hairy cell leukemia), symptoms, treatment, side effects of treatment (including learning problems), and the expected future direction of…

Frank hematuria as the presentation feature of acute leukemia

Directory of Open Access Journals (Sweden)

Suriya Owais

2010-01-01

Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

Directory of Open Access Journals (Sweden)

AnnaMaria Nosari

2012-11-01

Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

Diagnosis and treatment of leukemia recognized in atomic-bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Ichimaru, M [Nagasaki Univ. (Japan). School of Medicine

1978-05-01

Out of atomic bomb survivors in Hiroshima and Nagasaki, 256 patients which were diagnosed as having leukemia by 1975 and of which exposure dose was estimated as over 1 rad were described. Chronic myelocytic leukemia (CGL) was plentiful in Hiroshima, and acute myelocytic leukemia (AGL) was comparatively plentiful in Nagasaki. Chronic lymphatic leukemia (CLL) was not recognized in the atomic bomb survivors exposed at places near the center of the explosion, but CLL was recognized plentifully in the atomic bomb survivors exposed to radiation of under 1 rad. The incidence of leukemia according to the total dose was higher in Hiroshima than in Nagasaki. When RBE of neutron on the occurrence of leukemia was considered to be five times that of gamma-ray, the occurrence curves in both cities were consistent well. As to a relationship between leukemia in the atomic bomb survivors and the age at the exposure time, CGL occurred early in the atomic bomb survivors exposed at an early age. A specific lesion of leukemia in the atomic bomb survivors was not recognized, but cases of which leukemia cells were negative to peroxidase and were very difficult to be identified were plentiful in the atomic bomb survivors exposed within 2 km from the explosion center. The treatment of leukemia in atomic bomb survivors does not differ from that of general leukemia, but a method of treatment, administration dosage, a method and a kind of supportive care must be discussed according to each case.

The MLL recombinome of acute leukemias in 2013

DEFF Research Database (Denmark)

Meyer, C; Hofmann, Julian; Burmeister, T

2013-01-01

patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79......Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia...... patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All...

Leukemia in atomic bomb survivors. 1. General observations. Leukemia in survivors of atomic bombing. Cytologic and biochemical studies on the granulocytes in early leukemia among atomic bomb survivors. Leukemogenic effects of ionizing radiation on atomic bomb survivors in Hiroshima City

Energy Technology Data Exchange (ETDEWEB)

Lange, R D; Moloney, W C; Yamawaki, Tokuso; Kastenbaum, M A

1959-01-01

This document contains 4 separate reports on leukemia in survivals of the atomic explosions in Hiroshima and Nagasaki. In the first report, observations on seventy-five established cases of leukemia occurring in people exposed to atomic bomb radiation are presented. These data indicate a great increase in the incidence of leukemia among atomic bomb survivors due to a single massive exposure to ionizing radiation. The leukemogenic effects of radiation are manifested equally in both sexes and at all age levels represented in this series. The striking preponderance of chronic myelogenous leukemia compared to chronic lymphatic leukemia has been noted in exposed individuals but it is pointed out that chronic lymphatic leukemia is comparatively rare among the Japanese. Cases of leukemia are still appearing in atomic bomb survivors. However, since 1950 there has been a steady decline in the number of cases. The second report consists of a review of all cases of leukemia referred to the ABCC from 1948 to April 1952, a total of 75 cases. In the third report, hematological and biochemical findings in separated leukocytes of four cases of preclinical myelogenous leukemia developing in atomic bomb survivors are described. The incidence of leukemia among survivors in Hiroshima is the topic of the fourth report. 38 references, 8 figures, 10 tables.

Leukemia among participants in military maneuvers at a nuclear bomb test

International Nuclear Information System (INIS)

Caldwell, G.G.; Kelley, D.B.; Heath, C.W.

1980-01-01

To test the possibility of a casual relationship between leukemia and exposure to nuclear radiation, the frequency of leukemia in personnel observing the detonation of a nuclear device called ''Smoky'' during August 1957 was determined. Of some 3224 men who witnessed the detonation, nine cases of leukemia were observed. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, one of hairy cell lymphocyctic leukemia, and one of acute lymphocytic luekemia. These findings represent a significant increase over the expected leukemia incidence of 3.5 cases. Mean film-badge gamma radiation dose for the study group was 466.2 mrem

Induction of immune resistance against L1210 lymphatic leukemia in mice after chemoradiotherapy of the leukemia and reconstitution with bone marrow purged from the leukemia with mafosfamide

International Nuclear Information System (INIS)

Skorski, T.; Kawalec, M.

1988-01-01

Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously ex vivo purged of the leukemia cells with mafosfamide (ASTA Z7654) and stored in liquid nitrogen. Eight weeks after cytoreductive therapy and bone marrow transplantation we tried to immunize the mice against the lethal dose of the leukemia by i.p. injections of L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth). About 75% of such mice were able to reject the subsequent 10(3) L1210 leukemia cell challenge, as compared with 70% of normal immunized mice and 55% of mice reconstituted with bone marrow cells not treated with mafosfamide

Molecular biomarkers for the study of childhood leukemia

International Nuclear Information System (INIS)

Smith, Martyn T.; McHale, Cliona M.; Wiemels, Joseph L.; Zhang, Luoping; Wiencke, John K.; Zheng, Shichun; Gunn, Laura; Skibola, Christine F.; Ma, Xiaomei; Buffler, Patricia A.

2005-01-01

Various specific chromosome rearrangements, including t(8;21), t(15;17), and inv(16), are found in acute myeloid leukemia (AML) and in childhood acute lymphocytic leukemia (ALL), t(12;21) and t(1;19) are common. We sequenced the translocation breakpoints of 56 patients with childhood ALL or AML harboring t(12;21), t(8;21), t(15;17), inv(16), and t(1;19), and demonstrated, with the notable exception of t(1;19), that these rearrangements are commonly detected in the neonatal blood spots (Guthrie cards) of the cases. These findings show that most childhood leukemias begin before birth and that maternal and perinatal exposures such as chemical and infectious agents are likely to be critical. Indeed, we have reported that exposure to indoor pesticides during pregnancy and the first year of life raises leukemia risk, but that later exposures do not. We have also examined aberrant gene methylation in different cytogenetic subgroups and have found striking differences between them, suggesting that epigenetic events are also important in the development of some forms of childhood leukemia. Further, at least two studies now show that the inactivating NAD(P)H:quinone acceptor oxidoreductase (NQO1) C609T polymorphism is positively associated with leukemias arising in the first 1-2 years of life and polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been associated with adult and childhood ALL. Thus, low folate intake and compounds that are detoxified by NQO1 may be important in elevating leukemia risk in children. Finally, we are exploring the use of proteomics to subclassify leukemia, because cytogenetic analysis is costly and time-consuming. Several proteins have been identified that may serve as useful biomarkers for rapidly identifying different forms of childhood leukemia

Genetics Home Reference: chronic myeloid leukemia

Science.gov (United States)

... Central Quintás-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc. 2006 Jul;81(7):973-88. Review. Citation on PubMed Skorski T. Genetic mechanisms of chronic myeloid leukemia blastic transformation. Curr Hematol Malig Rep. 2012 Jun; ...

Treatment-associated leukemia following testicular cancer

NARCIS (Netherlands)

Travis, LB; Andersson, M; Gospodarowicz, M; van Leeuwen, FE; Bergfeldt, K; Lynch, CF; Curtis, RE; Kohler, BA; Wiklund, T; Storm, H; Holowaty, E; Hall, P; Pukkala, E; Sleijfer, DT; Clarke, EA; Boice, JD; Stovall, M; Gilbert, E

2000-01-01

Background: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. Methods: Within a

Chronic Myelogenous Leukemia (CML) (For Parents)

Science.gov (United States)

... studying the leukemia cells collected from the blood, bone marrow, and/or spinal fluid, doctors can determine the type of leukemia a child has. This is important because treatment varies among different types ... blood or bone marrow, doctors can tell whether the Philadelphia chromosome is ...

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

Science.gov (United States)

Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

2016-05-01

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

Answer to the comments made by N. Gibson, H. Rauscher and G. Roebben on the article by A.J. Lecloux (J Nanopart Res (2015) 17:447) regarding the use of the volume-specific surface area (VSSA) to classify nanomaterials

Energy Technology Data Exchange (ETDEWEB)

Lecloux, André J., E-mail: envicat@skynet.be [ENVICAT Consulting (Belgium)

2016-08-15

This article is an answer to the comments made by N. Gibson, H. Rauscher and G. Roebben on the article by Lecloux (J Nanopart Res 17:447, 2015) regarding the use of the volume-specific surface area (VSSA) to classify nanomaterials. The key point of discussion is the comparison of two models. The VSSA concept, developed for monodispersed spherical non-porous particle size distribution, was applied in two different ways to calculate the VSSA corresponding to a poly-dispersed distribution of particle size: on one side, a total VSSA value that is the number-weighted sum of the individual VSSAs corresponding to each particle size present with its frequency in the distribution. On the other side, a weight-averaged VSSA based on the measurement method, dividing the total surface area of all the particles by their total volume. The key questions are which model is better representing the experimental VSSA values obtained by analysis of the nitrogen adsorption isotherms and which model is the most appropriate to identify nanomaterials? This cannot be answered on a theoretical basis. Only a comparison with various experimental data could decide which model is the most appropriate.

Childhood Leukemia

Science.gov (United States)

... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

Leukemia after therapy with alkylating agents for childhood cancer

International Nuclear Information System (INIS)

Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

1987-01-01

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

Proceedings of the symposium on leukemia clustering

Energy Technology Data Exchange (ETDEWEB)

Elaguppillai, V [Atomic Energy Control Board, Ottawa, ON (Canada); Goyette, J P [Atomic Energy Control Board, Ottawa, ON (Canada). Advisory Committee on Radiological Protection; Hill, G; Krewski, D [Department of National Health and Welfare, Ottawa, ON (Canada); Osborne, R V [Atomic Energy of Canada Ltd., Chalk River, ON (Canada). Chalk River Nuclear Labs.

1992-07-01

Clusters of leukemia in populations living in specific locations in various countries have been examined by scientific and medical experts for many years. In general, the reason for the existence of these clusters is unknown. The recent discovery of a small cluster of leukemias among children who were born in the vicinity of a nuclear fuel reprocessing facility in England has stimulated wide interest in the possible occurrence of clusters of leukemia around nuclear facilities. The purpose of this symposium was to present scientific evidence concerning the existence of leukemia clusters in the population, to discuss possible causes for these clusters and to suggest directions for future research. Distinguished speakers from Canada, the United Kingdom, Germany, Italy and the U.S.A. participated in this symposium. (author).

Proceedings of the symposium on leukemia clustering

International Nuclear Information System (INIS)

Elaguppillai, V.; Goyette, J.P.; Osborne, R.V.

1992-07-01

Clusters of leukemia in populations living in specific locations in various countries have been examined by scientific and medical experts for many years. In general, the reason for the existence of these clusters is unknown. The recent discovery of a small cluster of leukemias among children who were born in the vicinity of a nuclear fuel reprocessing facility in England has stimulated wide interest in the possible occurrence of clusters of leukemia around nuclear facilities. The purpose of this symposium was to present scientific evidence concerning the existence of leukemia clusters in the population, to discuss possible causes for these clusters and to suggest directions for future research. Distinguished speakers from Canada, the United Kingdom, Germany, Italy and the U.S.A. participated in this symposium. (author)

Genetics Home Reference: core binding factor acute myeloid leukemia

Science.gov (United States)

... binding factor acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Goyama S, Mulloy JC. Molecular ...

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Science.gov (United States)

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki

2015-01-01

Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34+CD38+CD19+ and CD34−CD19+ cells initiated leukemia, and in MLL-AF9 patients, CD34−CD19+ cells were LICs. In MLL-ENL patients, either CD34+ or CD34− cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34+CD38−CD19−CD33− cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34+CD38−CD19−CD33− cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4+ single positive (SP), CD8+ SP, and CD4+CD8+ double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34+CD38+ and CD34− LICs but not in CD34+CD38−CD19−CD33− HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

Ultra-sensitive detection of leukemia by graphene

Science.gov (United States)

Akhavan, Omid; Ghaderi, Elham; Hashemi, Ehsan; Rahighi, Reza

2014-11-01

Graphene oxide nanoplatelets (GONPs) with extremely sharp edges (lateral dimensions ~20-200 nm and thicknesses leukemia cells. The blood serums containing the extracted guanine were used in differential pulse voltammetry (DPV) with reduced graphene oxide nanowall (rGONW) electrodes to develop fast and ultra-sensitive electrochemical detection of leukemia cells at leukemia fractions (LFs) of ~10-11 (as the lower detection limit). The stability of the DPV signals obtained by oxidation of the extracted guanine on the rGONWs was studied after 20 cycles. Without the guanine extraction, the DPV peaks relating to guanine oxidation of normal and abnormal cells overlapped at LFs diagnosis.Graphene oxide nanoplatelets (GONPs) with extremely sharp edges (lateral dimensions ~20-200 nm and thicknesses leukemia cells. The blood serums containing the extracted guanine were used in differential pulse voltammetry (DPV) with reduced graphene oxide nanowall (rGONW) electrodes to develop fast and ultra-sensitive electrochemical detection of leukemia cells at leukemia fractions (LFs) of ~10-11 (as the lower detection limit). The stability of the DPV signals obtained by oxidation of the extracted guanine on the rGONWs was studied after 20 cycles. Without the guanine extraction, the DPV peaks relating to guanine oxidation of normal and abnormal cells overlapped at LFs diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/C4NR04589K

Targeting neuropilin-1 in human leukemia and lymphoma.

Science.gov (United States)

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos E; Zurita, Amado J; Kuniyasu, Akihiko; Eckhardt, Bedrich L; Marini, Frank C; Lichtiger, Benjamin; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2011-01-20

Targeted drug delivery offers an opportunity for the development of safer and more effective therapies for the treatment of cancer. In this study, we sought to identify short, cell-internalizing peptide ligands that could serve as directive agents for specific drug delivery in hematologic malignancies. By screening of human leukemia cells with a combinatorial phage display peptide library, we isolated a peptide motif, sequence Phe-Phe/Tyr-Any-Leu-Arg-Ser (F(F)/(Y)XLRS), which bound to different leukemia cell lines and to patient-derived bone marrow samples. The motif was internalized through a receptor-mediated pathway, and we next identified the corresponding receptor as the transmembrane glycoprotein neuropilin-1 (NRP-1). Moreover, we observed a potent anti-leukemia cell effect when the targeting motif was synthesized in tandem to the pro-apoptotic sequence (D)(KLAKLAK)₂. Finally, our results confirmed increased expression of NRP-1 in representative human leukemia and lymphoma cell lines and in a panel of bone marrow specimens obtained from patients with acute lymphoblastic leukemia or acute myelogenous leukemia compared with normal bone marrow. These results indicate that NRP-1 could potentially be used as a target for ligand-directed therapy in human leukemias and lymphomas and that the prototype CGFYWLRSC-GG-(D)(KLAKLAK)₂ is a promising drug candidate in this setting.

Identification of an MLC suppressor cell population in acute leukemia

International Nuclear Information System (INIS)

Bryan, C.F.; Broxmeyer, H.E.; Hansen, J.; Pollack, M.; Dupont, B.

1978-01-01

The MLC data from the 20 nonsuppressing patients and the 10 suppressing leukemia patients were analyzed with regard to HLA-A, -B, and -C antigens in the leukemia patients and compared with the presence or absence of suppression. These results demonstrate a significant increase (p < 0.02, Mann-Whitney U test) of HLA antigens Al, A3, and A11 in the leukemia suppressor group. Seven of the 10 leukemia patients showing suppression were A1, A3, or A11, while only 4 of the 20 nonsuppressing leukemia patients carried any of these three HLA-A antigens. The studies demonstrate that a nonspecific suppression of MLC responses is observed in 33% of the patients with acute leukemia

Characterization of leukemias with ETV6-ABL1 fusion

Science.gov (United States)

Zaliova, Marketa; Moorman, Anthony V.; Cazzaniga, Giovanni; Stanulla, Martin; Harvey, Richard C.; Roberts, Kathryn G.; Heatley, Sue L.; Loh, Mignon L.; Konopleva, Marina; Chen, I-Ming; Zimmermannova, Olga; Schwab, Claire; Smith, Owen; Mozziconacci, Marie-Joelle; Chabannon, Christian; Kim, Myungshin; Frederik Falkenburg, J. H.; Norton, Alice; Marshall, Karen; Haas, Oskar A.; Starkova, Julia; Stuchly, Jan; Hunger, Stephen P.; White, Deborah; Mullighan, Charles G.; Willman, Cheryl L.; Stary, Jan; Trka, Jan; Zuna, Jan

2016-01-01

To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with

Understanding Leukemia

Science.gov (United States)

... for as long as they take it. Allogeneic stem cell transplantation is another treatment option that is only done if CML is not responding as expected to drug therapy. Chronic Lymphocytic Leukemia (CLL) . Some CLL patients do not need treatment ...

Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

Science.gov (United States)

Hittelman, W N; Broussard, L C; McCredie, K

1979-11-01

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

Science.gov (United States)

Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

2018-03-11

Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

The role of peptide and DNA vaccines in myeloid leukemia immunotherapy

Directory of Open Access Journals (Sweden)

Lin Chen

2013-02-01

Full Text Available Abstract While chemotherapy and targeted therapy are successful in inducing the remission of myeloid leukemia as acute myeloid leukemia (AML and chronic myeloid leukemia (CML, the disease remains largely incurable. This observation is likely due to the drug resistance of leukemic cells, which are responsible for disease relapse. Myeloid leukemia vaccines may most likely be beneficial for eradicating minimal residual disease after treatment with chemotherapy or targeted therapy. Several targeted immunotherapies using leukemia vaccines have been heavily investigated in clinical and preclinical trials. This review will focus on peptides and DNA vaccines in the context of myeloid leukemias, and optimal strategies for enhancing the efficacy of vaccines based on myeloid leukemia immunization are also summarized.

Blastic Plasmacytoid Dendritic Cell Leukemia in a Black Malian

African Journals Online (AJOL)

2017-06-28

Jun 28, 2017 ... BPDCN in Mali. KEYWORDS: Acute Leukemia, black african, dendritic cell, Mali ... myeloid neoplasm by the 2008 world health organization classification of .... There are many standardized treatment regimens, and many protocols with ... leukemia chemotherapy regimen[7,11] or chronic leukemia treatment ...

Hepatitis viral aguda

Directory of Open Access Journals (Sweden)

Héctor Rubén Hernández Garcés

1998-10-01

Full Text Available Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, and the complementary examinations with special emphasis on the viral markers and the positive diagnosis were also considered

Virale commercials: de consument als marketeer. Onderzoek naar de redenen waarom consumenten virale commercials doorsturen: hun motieven, de inhoudskenmerken van viral commercials en de mediumcontext waarin virale commercials verschijnen

NARCIS (Netherlands)

Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

2010-01-01

Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

Science.gov (United States)

Straus, D J; Mertelsmann, R; Koziner, B; McKenzie, S; de Harven, E; Arlin, Z A; Kempin, S; Broxmeyer, H; Moore, M A; Menendez-Botet, C J; Gee, T S; Clarkson, B D

1980-11-01

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Expression and role of DJ-1 in leukemia

International Nuclear Information System (INIS)

Liu Hang; Wang Min; Li Min; Wang Donghai; Rao Qing; Wang Yang; Xu Zhifang; Wang Jianxiang

2008-01-01

DJ-1 is a multifunctional protein that has been implicated in pathogenesis of some solid tumors. In this study, we found that DJ-1 was overexpressed in acute leukemia (AL) patient samples and leukemia cell lines, which gave the first clue that DJ-1 overexpression might be involved in leukemogenesis and/or disease progression of AL. Inactivation of DJ-1 by RNA-mediated interference (RNAi) in leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation potential and enhancement of the sensitivity of leukemia cells to chemotherapeutic drug etoposide. Further investigation of DJ-1 activity revealed that phosphatase and tensin homolog (PTEN), as well as some proliferation and apoptosis-related genes, was regulated by DJ-1. Thus, DJ-1 might be involved in leukemogesis through regulating cell growth, proliferation, and apoptosis. It could be a potential therapeutic target for leukemia

Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

Directory of Open Access Journals (Sweden)

RAIMON eDURAN-STRUUCK

2015-11-01

Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

Treatment of Aggressive NK-Cell Leukemia

DEFF Research Database (Denmark)

Boysen, Anders Kindberg; Jensen, Paw; Johansen, Preben

2011-01-01

Aggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic...... literature concerning treatment of aggressive NK-cell leukemia....

Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

Science.gov (United States)

De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

2014-01-01

ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

Viral Disease Networks?

Science.gov (United States)

Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

2010-03-01

Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

The biology and targeting of FLT3 in pediatric leukemia

Directory of Open Access Journals (Sweden)

Colleen eAnnesley

2014-09-01

Full Text Available Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high risk groups of acute myeloid leukemia (AML and acute lymphoblastic leukemia (ALL, as well as for relapsed leukemia, remains poor. Intensified chemotherapy regimens have somewhat improved success rates, but at the cost of drastically increased morbidity and long term adverse effects. With the success of imatinib in Philadelphia-chromosome positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over the past 15 years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3. FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high risk pediatric AML and in certain high risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy.

Radiogenic leukemia risk analysis for the Techa River Cohort members

International Nuclear Information System (INIS)

Krestinina, L.Y.; Epifanova, S.B.; Akleyev, A.V.; Preston, D.; Davis, F.; Ron, E.

2008-01-01

Full text: Members of the Techa River Cohort have been exposed to a long-term external and internal irradiation due to releases of radioactive waste from the Mayak Production Association into the Techa River. Since internal exposure resulted primarily from incorporation of 90 Sr in the bone structure, the bone marrow was the principal target. The maximum dose to the red bone marrow accumulated over 50 years in cohort members reached 2 Gy, and the mean dose was 0.3 Gy. The epidemiological analysis of radiogenic risk of leukemia development was conducted based on the retrospective cohort study approach and regression analysis using the Epicure statistical packet. The extended Techa River Cohort (ETRC) includes about 30 thousand people of the two genders, various ages and different ethnicity (mostly Russians, Tartars and Bashkirs). The catchment area for leukemia mortality and incidence follow-up includes the whole Chelyabinsk and Kurgan Oblasts. The previous analysis of leukemia mortality risk for a 50-year follow-up period pointed out statistically significant dose dependence. The presentation will for the first time describe the results of leukemia incidence risk analyses for the period from 1953 through 2004. Over this 52-year follow-up period 92 leukemia cases (42 in men and 50 in women) were registered among ETRC members resident in the catchment area. Among those 92 cases there were 22 cases attributed to chronic lymphoid leukemia (12 in men and 10 in women). The preliminary analysis of leukemia incidence risk showed a statistically significant linear dependence on dose for total leukemias (p = 0.006), as well as for leukemias with CLL excluded (p < 0.001). The point value of the total leukemia incidence ERR was 2.0/Gy (95% CI: 0.4-15.4) and for leukemia with CLL excluded the ERR was 4.5/Gy (95% CI: 1.1-14.7). More than 57% of leukemia cases (excluding CLL) registered in ETRC members could be related to the radiogenic factor. Analyses of chronic lymphoid

Gastrointestinal complications of leukemia and its treatment

International Nuclear Information System (INIS)

Hunter, T.B.; Bjelland, J.C.

1984-01-01

Leukemia represents 4% of all cancer deaths and is the leading cause of death from malignancy for all patients under 30 years of age. Various rare, usually preterminal gastrointestinal complications of leukemia have been reported. These complications are becoming more common and no longer should be considered unusual. Their increasing incidence is the result of new, more aggressive treatment methods and increased patient lifespan. The authors describe the relative incidence and common radiographic presentations of leukemia-related gastrointestinal disease and emphasize that its prognosis is favorable with prompt diagnosis and treatment

Fungal natural products targeting chronic lymphocytic leukemia

DEFF Research Database (Denmark)

Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

2012-01-01

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds......,3 This includes analysis of the spectroscopic data generated from LC-DAD-MS to reveal whether the active principles are either structurally known compounds or are likely to be novel compounds. This paper will illustrate our integrated discovery approaches and recent findings of anti-leukemia compounds....

Phase II trial of vindesine in patients with acute leukemia.

Science.gov (United States)

Sklaroff, R B; Arlin, Z; Young, C W

1979-01-01

Vindesine was administered to 18 patients with acute leukemia who had failed conventional chemotherapy. Each course of therapy consisted of an iv bolus infusion at a dose of 1-2 mg/m2 given daily x 5-10 days. Of 13 patients with acute lymphoblastic leukemia, two had partial remissions which lasted 2 and 3 months and five had minor responses. One of three patients with acute nonlymphoblastic leukemia and one of two patients with blastic crisis of chronic myelogenous leukemia each had a minor response. The data suggest that vindesine has activity in the treatment of acute leukemia.

Late effects of childhood leukemia therapy.

Science.gov (United States)

Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J

2011-09-01

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

Adult T-cell leukemia-associated antigen (ATLA) and anti-ATLA antibodies in patients with Hodgkin's disease in the Nagasaki District.

Science.gov (United States)

Kinoshita, K; Amagasaki, T; Yamada, Y; Ikeda, S; Momita, S; Toriya, K; Kamihira, S; Ichimaru, M

1983-01-01

Seven patients with Hodgkin's disease in the Nagasaki district were examined for adult T-cell leukemia-associated antigen (ATLA), a human retrovirus-associated antigen, and anti-ATLA antibodies. Anti-ATLA antibody reactivity with the ATLA-positive cultured cells from an ATL patient was demonstrated in four (57.1%) of seven patients. This suggests that infection by a human retrovirus may be closely associated with Hodgkin's disease in the Nagasaki district. However, ATLA could not be induced in the cultured mononuclear cells taken from biopsied lymph nodes of the three patients examined. Hence, it is necessary to collect more direct evidence in the search for a viral etiology of Hodgkin's disease.

Mobil Viral Pazarlama

OpenAIRE

Barutçu, Süleyman

2011-01-01

OBJECTIVE: Mobile Viral Marketing, with using mobile phones, is one of the most importantinnovations after Word of Mouth Marketing performed by face to face amongpeople and Viral Marketing performed in the İnternet. The main objective of thisstudy is to call marketing communicators’ and academicians’ attentions whowant to increase the recognition of companies’ products, services and brands tobecome a current issue in the marketplace using Mobile Viral Marketingapplications by reason of techno...

Dose-response relationship of neutrons and γ rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971

International Nuclear Information System (INIS)

Ishimaru, T.; Otake, M.; Ichimaru, M.

1979-01-01

The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and γ kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by γ and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from γ rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with γ radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to γ rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

Science.gov (United States)

2017-08-29

Acute Lymphoblastic Leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hemophagocytic Lymphohistiocytosis (HLH); Familial Hemophagocytic Lymphohistiocytosis (FLH); Viral-associated Hemophagocytic Syndrome (VAHS); X-linked Lymphoproliferative Disease (XLP)

Plasminogen activator inhibitor-2 in patients with monocytic leukemia.

Science.gov (United States)

Scherrer, A; Kruithof, E K; Grob, J P

1991-06-01

Plasma and tumor cells from 103 patients with leukemia or lymphoma at initial presentation were investigated for the presence of plasminogen activator inhibitor-2 (PAI-2) antigen, a potent inhibitor of urokinase. PAI-2 was detected in plasma and leukemic cells of the 21 patients with leukemia having a monocytic component [acute myelomonocytic (M4), acute monoblastic (M5), and chronic myelomonocytic leukemias], and in the three patients with acute undifferentiated myeloblastic leukemia (M0). In contrast, this serine protease inhibitor was undetectable in 79 patients with other subtypes of acute myeloid leukemia or other hematological malignancies. Serial serum PAI-2 determinations in 16 patients with acute leukemia at presentation, during therapy, remission, and relapse revealed that in the five patients with M4-M5, elevated PAI-2 levels rapidly normalized under therapy and during remission, but increased again in the patients with a relapse associated with an M4-M5 phenotype. Thus, PAI-2 seems to be a marker highly specific for the active stages of monocytic leukemia, i.e. presentation and relapse. The presence of PAI-2 in the plasma and cells of patients with M0 may give a clue to a monocytic origin of these cells.

Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

DEFF Research Database (Denmark)

Schmiegelow, K; Nyvold, C; Seyfarth, J

2001-01-01

Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone......, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction...... pronounced when B cell precursor and T cell leukemia were analyzed separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47, P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P = 0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients...

Chronic myeloid leukemia: reminiscences and dreams

Science.gov (United States)

Mughal, Tariq I.; Radich, Jerald P.; Deininger, Michael W.; Apperley, Jane F.; Hughes, Timothy P.; Harrison, Christine J.; Gambacorti-Passerini, Carlo; Saglio, Giuseppe; Cortes, Jorge; Daley, George Q.

2016-01-01

With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic myeloid leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people’s lives. This tribute provides an outline of the remarkable story of chronic myeloid leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman. PMID:27132280

Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

Directory of Open Access Journals (Sweden)

Ikebuchi Ryoyo

2011-09-01

Full Text Available Abstract The inhibitory receptor programmed death-1 (PD-1 and its ligand, programmed death-ligand 1 (PD-L1 are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

International Nuclear Information System (INIS)

Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula

2009-01-01

Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance

The contribution of benzene to smoking-induced leukemia.

OpenAIRE

Korte, J E; Hertz-Picciotto, I; Schulz, M R; Ball, L M; Duell, E J

2000-01-01

Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts t...

Understanding Image Virality

Science.gov (United States)

2015-06-07

Example non-viral images. Figure 1: Top: Images with high viral scores in our dataset depict internet “celebrity” memes ex. “Grumpy Cat”; Bottom: Images...of images that is most similar to ours is the concurrently introduced viral meme generator of Wang et al., that combines NLP and Computer Vision (low...doing any of our tasks. The test included questions about widely spread Reddit memes and jargon so that anyone familiar with Reddit can easily get a high

Interaction between C/EBPβ and Tax down-regulates human T-cell leukemia virus type I transcription

International Nuclear Information System (INIS)

Hivin, P.; Gaudray, G.; Devaux, C.; Mesnard, J.-M.

2004-01-01

The human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral transcription through three imperfect tandem repeats of a 21-bp sequence called Tax-responsive element (TxRE). Tax regulates transcription via direct interaction with some members of the activating transcription factor/CRE-binding protein (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP domain, Tax stimulates the binding of these cellular factors to the CRE-like sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer binding protein β (C/EBPβ) forms stable complexes on the CRE site in the presence of CREB-2. Given that C/EBPβ has also been found to interact with Tax, we analyzed the effects of C/EBPβ on viral Tax-dependent transcription. We show here that C/EBPβ represses viral transcription and that Tax is no more able to form a stable complex with CREB-2 on the TxRE site in the presence of C/EBPβ. We also analyzed the physical interactions between Tax and C/EBPβ and found that the central region of C/EBPβ, excluding its ZIP domain, is required for direct interaction with Tax. It is the first time that Tax is described to interact with a basic leucine-zipper (bZIP) factor without recognizing its ZIP domain. Although unexpected, this result explains why C/EBPβ would be unable to form a stable complex with Tax on the TxRE site and could then down-regulate viral transcription. Lastly, we found that C/EBPβ was able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone. In conclusion, we propose that during cell activation events, which stimulate the Tax synthesis, C/EBPβ may down-regulate the level of HTLV-I expression to escape the cytotoxic-T-lymphocyte response

Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Forester, Craig M.; Braunreiter, Chi L.; Yaish, Hasan; Afify, Zeinab; Hedlund, Gary L.

2009-01-01

In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

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Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

2009-11-15

In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

Science.gov (United States)

... Familial acute myeloid leukemia with mutated CEBPA Familial acute myeloid leukemia with mutated CEBPA Printable PDF Open All Close ... on PubMed (1 link) PubMed OMIM (1 link) LEUKEMIA, ACUTE MYELOID Sources for This Page Carmichael CL, Wilkins EJ, ...

Do We Know What Causes Chronic Myeloid Leukemia?

Science.gov (United States)

... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

The Danish National Chronic Lymphocytic Leukemia Registry

DEFF Research Database (Denmark)

da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

2016-01-01

AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

Childhood acute lymphoblastic leukemia: from genome to patient

International Nuclear Information System (INIS)

Kolenova, A.

2016-01-01

Acute lymphoblastic leukemia is the most common malignant disease in childhood. During recent decades prognosis for children with acute leukemia has greatly improved, including the patients treated in the Slovak Republic. The prognosis for these patients has improved as a result of the systematic and well-organized international research efforts and clinical trials. The advent of new genomic technologies has provided new insights into leukemogenesis, identified many novel subtypes of leukemia, and triggered development of new therapeutic formulations. The success of treatment depends on stratifying patients into risk group and incorporating novel treatment strategies.The Slovak pediatric leukemia group is actively incorporated into these international clinical trials and the outcome for our patients is comparable to the results published in Western Europe. (author)

Circumvention of glucocorticoid resistance in childhood leukemia.

Science.gov (United States)

Haarman, E G; Kaspers, G J L; Pieters, R; Rottier, M M A; Veerman, A J P

2008-09-01

In this study, we determined if in vitro resistance to prednisolone and dexamethasone could be circumvented by cortivazol or methylprednisolone, or reversed by meta-iodobenzylguanidine in pediatric lymphoblastic and myeloid leukemia. As there were strong correlations between the LC50 values (drug concentration inducing 50% leukemic cell kill, LCK) of the different glucocorticoids and median prednisolone/methylprednisolone, prednisolone/dexamethasone and prednisolone/cortivazol LC50 ratios did not differ between the leukemia subtypes, we conclude that none of the glucocorticoids had preferential anti-leukemic activity. Meta-iodobenzylguanidine however, partially reversed glucocorticoid resistance in 19% of the lymphoblastic leukemia samples.

Occupation, hobbies, and acute leukemia in adults.

Science.gov (United States)

Terry, Paul D; Shore, David L; Rauscher, Garth H; Sandler, Dale P

2005-10-01

Occupational and industrial exposures have been implicated in the etiology of leukemia, yet uncertainty remains regarding potential high risk occupations. We examined the associations between self-reported occupations and hobbies and acute leukemia risk using data from 811 cases and 637 controls participating in a case-control study in the U.S. and Canada. We found that several occupations may increase the risk of acute leukemia, particularly occupations related to petroleum products, rubber, nuclear energy, munitions, plastics, and electronics manufacturing. Differences were noted according to histological type. Other occupations and hobbies were not clearly associated with risk.

Clinical Presentations of Acute Leukemia

International Nuclear Information System (INIS)

Shahab, F.; Raziq, F.

2014-01-01

Objective: To document the clinical presentation and epidemiology of various types of acute leukemia with their respective referral source at a tertiary level centre in Peshawar. Study Design: An observational study. Place and Duration of Study: Department of Pathology, Hayatabad Medical Complex (HMC), Peshawar, from January 2011 to May 2012. Methodology: A total of 618 bone marrow biopsy reports were reviewed. All biopsy reports labeled as acute leukemia were reviewed for age, gender, address, referring unit, diagnosis on bone marrow examination, presenting complaints, duration of illness and findings of clinical examination. Results: Ninety-two patients were diagnosed as suffering from acute leukemias (15%). ALL was most prevalent (46%), followed by AML (38%) and undifferentiated acute leukemia (16%). Males were affected more compared to females (60% vs. 40%). ALL and AML were predominant in pediatric (64%) and adults (77%) patients respectively. Patients from Afghanistan accounted for 33% of all cases followed by Peshawar (14%). Fever (77%), pallor (33%) and bleeding disorders (23%) were the main presenting complaints. Enlargement of liver, spleen and lymph nodes together was associated with ALL compared with AML (p = 0.004). Conclusion: ALL-L1 and AML-M4 were the most common sub-types. Fever, pallor and bleeding disorders were the main presenting complaints. Enlargement of liver, spleen and lymph nodes was more frequently associated with ALL compared to AML. (author)

Marijuana Smoking in Patients With Leukemia.

Science.gov (United States)

Khwaja, Sara; Yacoub, Abraham; Cheema, Asima; Rihana, Nancy; Russo, Robin; Velez, Ana Paula; Nanjappa, Sowmya; Sandin, Ramon L; Bohra, Chandrashekar; Gajanan, Ganesh; Greene, John N

2016-07-01

Worldwide, marijuana (cannabis) is a widely used drug. The incidence of marijuana smoking is increasing and is second only to tobacco as the most widely smoked substance in the general population. It is also the second most commonly used recreational drug after alcohol. Some adverse effects of marijuana smoking have been documented; however, the number of studies on the pulmonary effects of marijuana in individuals with leukemia is limited. In our case series, we report on 2 men with acute myeloid leukemia with miliary nodular lung patterns on computed tomography of the chest due to heavy marijuana use. We also report on 2 patients with acute lymphocytic leukemia who had a history of smoking marijuana and then developed lung opacities consistent with mold infection.

The MLL recombinome of acute leukemias in 2017

DEFF Research Database (Denmark)

Meyer, C; Burmeister, T; Gröger, D

2018-01-01

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs)...... of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.Leukemia advance online publication, 8 August 2017; doi:10.1038/leu.2017.213....

Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

Energy Technology Data Exchange (ETDEWEB)

Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula [Ondokuz Mayis University, Samsun (Turkmenistan)

2009-10-15

Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance.

Resistance of human and mouse myeloid leukemia cells to UV radiation

International Nuclear Information System (INIS)

Poljak-Blazi, M.; Osmak, M.; Hadzija, M.

1989-01-01

Sensitivity of mouse bone marrow and myeloid leukemia cells and sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were the in vivo colony-forming ability of UV exposed cells and the inhibition of DNA synthesis during post-irradiation incubation for 24 h in vitro. Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m 2 ) and injected into x-irradiated animals did not form hemopoietic colonies on recipient's spleens, and recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia. In vitro, mouse bone marrow cells exhibited high sensitivity to UV light compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. (author)

PROGRESS IN ACUTE MYELOID LEUKEMIA

Science.gov (United States)

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

The discovery and early understanding of leukemia

NARCIS (Netherlands)

Kampen, Kim R.

The early history of leukemia reaches back 200 years. In 1811, Peter Cullen defined a case of splenitis acutus with unexplainable milky blood. Alfred Velpeau defined the leukemia associated symptoms, and observed pus in the blood vessels (1825). Alfred Donne detected a maturation arrest of the white

Modeling Human Leukemia Immunotherapy in Humanized Mice

Directory of Open Access Journals (Sweden)

Jinxing Xia

2016-08-01

Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

Genomic rearrangement in radiation-induced murine myeloid leukemia

International Nuclear Information System (INIS)

Ishihara, Hiroshi

1994-01-01

After whole body irradiation of 3Gy X ray to C3H/He male mice, acute myeloid leukemia is induced at an incidence of 20 to 30% within 2 years. We have studied the mechanism of occurrence of this radiation-induced murine myeloid leukemia. Detection and isolation of genomic structural aberration which may be accumulated accompanied with leukemogenesis are helpful in analyzing the complicated molecular process from radiation damage to leukemogenesis. So, our research work was done in three phases. First, structures of previously characterized oncogenes and cytokine-related genes were analyzed, and abnormal structures of fms(protooncogene encoding M-CSF receptor gene)-related and myc-related genes were found in several leukemia cells. Additionally, genomic structural aberration of IL-3 gene was observed in some leukemia cells, so that construction of genomic libraries and cloning of the abnormal IL-3 genomic DNAs were performed to characterize the structure. Secondly, because the breakage of chromosome 2 that is frequently observed in myeloid leukemia locates in proximal position of IL-1 gene cluster in some cases, the copy number of IL-1 gene was determined and the gene was cloned. Lastly, the abnormal genome of leukemia cell was cloned by in-gel competence reassociation method. We discussed these findings and evaluated the analysis of the molecular process of leukemogenesis using these cloned genomic fragments. (author)

TARGETED NANOPARTICLES FOR PEDIATRIC LEUKEMIA THERAPY

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Riyaz eBasha

2014-05-01

Full Text Available The two major forms of leukemia, acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML account for about one third of the malignancies diagnosed in children. Despite the marked successes in ALL and AML treatment, concerns remain regarding the occurrence of resistant disease in subsets of patients the residual effects of therapy that often persist for decades beyond the cessation of treatment. Therefore, new approaches are needed to reduce or to avoid off target toxicities, associated with chemotherapy and their long term residual effects. Recently, nanotechnology has been employed to enhance cancer therapy, via improving the bioavailability and therapeutic efficacy of anti-cancer agents. While in the last several years, numerous review articles appeared detailing the size, composition, assembly and performance evaluation of different types of drug carrying nanoparticles, the description and evaluation of lipoprotein based drug carriers have been conspicuously absent from most of these major reviews. The current review focuses on such information regarding nanoparticles with an emphasis on high density lipoprotein (HDL-based drug delivery systems to examine their potential role(s in the enhanced treatment of children with leukemia.

Case-control study of leukemia at a naval nuclear shipyard

International Nuclear Information System (INIS)

Stern, F.B.; Waxweiler, R.A.; Beaumont, J.J.

1986-01-01

A matched case-control study was conducted of 53 leukemia deaths and of 212 controls within a previously studied cohort of 24,545 on-shore workers employed between January 1, 1952 and August 15, 1977 at the Portsmouth (New Hampshire) Naval Shipyard. The study sought to ascertain a priori whether there was an association between leukemia deaths and occupational exposure to either ionizing radiation or organic solvents. To obtain information on individual exposures, radiation dose histories and detailed work histories by job and shop were evaluated for each subject. No statistically significant associations were found either between ionizing radiation or presumed solvent exposure and myelogenous or lymphatic leukemia. However, when specific job categories and shops were examined without benefit of a priori hypotheses, two occupations, electrician and welder, were found to be associated with leukemia. For electricians, the Mantel-Haenszel odds ratio (ORMH) was significantly elevated for all leukemias (ORMH = 3.00, 95% confidence interval (CI) = 1.29-6.98), particularly for lymphatic leukemia (ORMH = 6.00, 95% CI = 1.47-24.45). For welders, the odds ratio was not significantly elevated for all leukemias (ORMH = 2.25, 95% CI = 0.92-5.53), but was significantly elevated for myeloid leukemia (ORMH = 3.83, 95% CI = 1.28-11.46). These findings persisted when potential confounders were adjusted by means of a conditional logistic regression model

Childhood leukemia around nuclear facilities

International Nuclear Information System (INIS)

1991-01-01

This Information Bulletin highlights the conclusion made from an Atomic Energy Control Board of Canada (AECB) study on the incidence of childhood leukemia near nuclear facilities. All of the locations with the nuclear facilities are located in Ontario, the nuclear generating stations at Pickering and Bruce; the uranium mines and mills in Elliot Lake; the uranium refining facility in Port Hope; and nuclear research facilities located at Chalk River plus the small nuclear power plant in Rolphton. Two conclusions are drawn from the study: 1) while the rate of childhood leukemias made be higher or lower than the provincial average, there is no statistical evidence that the difference is due to anything but the natural variation in the occurrence of the disease; and 2) the rate of occurrence of childhood leukemia around the Pickering nuclear power station was slightly greater than the Ontario average both before and after the plant opened, but this, too , could be due to the natural variation

Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production

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De Camilli Pietro

2003-12-01

Full Text Available Abstract Background The retroviral Gag protein is the central player in the process of virion assembly at the plasma membrane, and is sufficient to induce the formation and release of virus-like particles. Recent evidence suggests that Gag may co-opt the host cell's endocytic machinery to facilitate retroviral assembly and release. Results A search for novel partners interacting with the Gag protein of the Moloney murine leukemia virus (Mo-MuLV via the yeast two-hybrid protein-protein interaction assay resulted in the identification of endophilin 2, a component of the machinery involved in clathrin-mediated endocytosis. We demonstrate that endophilin interacts with the matrix or MA domain of the Gag protein of Mo-MuLV, but not of human immunodeficiency virus, HIV. Both exogenously expressed and endogenous endophilin are incorporated into Mo-MuLV viral particles. Titration experiments suggest that the binding sites for inclusion of endophilin into viral particles are limited and saturable. Knock-down of endophilin with small interfering RNA (siRNA had no effect on virion production, but overexpression of endophilin and, to a lesser extent, of several fragments of the protein, result in inhibition of Mo-MuLV virion production, but not of HIV virion production. Conclusions This study shows that endophilins interact with Mo-MuLV Gag and affect virion production. The findings imply that endophilin is another component of the large complex that is hijacked by retroviruses to promote virion production.

Pupils with leukemia and their reintegration into school

OpenAIRE

Purkat, Maja

2013-01-01

One of the most common childhood malignancies is leukemia. Treatments are now much more successful than in the past, but many children with leukemia are facing difficulties when returning to school. For pupils with leukemia, school is very important, providing them with a feeling of normalcy and hope for the future. But when such a child, with all his or her characteristics, returns to school, he meets with certain requirements. He or she encounters obstacles which are directly or indirectly ...

Thymic irradiation and chronic myelogenous leukemia

International Nuclear Information System (INIS)

Shimaoka, K.; Sokal, J.E.

1977-01-01

Two cases of Ph positive chronic myelogenous leukemia with a history of thymic irradiation are presented. Both patients received radiation therapy from low voltage x-ray equipment at two to three months of age. Leukemia developed 18 and 22 years later. Presentation, response to antileukemic therapy, and clinical course did not differ from that of other patients with this disease treated in our department

Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo

Directory of Open Access Journals (Sweden)

Yuan-Chang Chang

2011-01-01

Full Text Available Emodin is one of major compounds in rhubarb (Rheum palmatum L., a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3 and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ΔΨm by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

Bile acids for viral hepatitis

DEFF Research Database (Denmark)

Chen, Weikeng; Liu, J; Gluud, C

2003-01-01

The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

Viral hemorrhagic septicemia

Science.gov (United States)

Batts, William N.; Winton, James R.

2012-01-01

Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

Science.gov (United States)

Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

1978-05-01

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

Birth weight and other perinatal characteristics and childhood leukemia in California.

Science.gov (United States)

Oksuzyan, S; Crespi, C M; Cockburn, M; Mezei, G; Kheifets, L

2012-12-01

We conducted a large registry-based study in California to investigate the association of perinatal factors and childhood leukemia with analysis of two major subtypes, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). We linked California cancer and birth registries to obtain information on 5788 cases and 5788 controls matched on age and sex (1:1). We examined the association of birth weight, gestational age, birth and pregnancy order, parental ages, and specific conditions during pregnancy and risk of total leukemia, ALL and AML using conditional logistic regression, with adjustment for potential confounders. The odds ratio (OR) per 1000 g increase in birth weight was 1.11 for both total leukemia and ALL. The OR were highest for babies weighing ≥ 4500 g with reference birth weight and LGA were associated with increased risk and SGA with decreased risk of total childhood leukemia and ALL, being first-born was associated with decreased risk of AML, and advanced paternal age was associated with increased risk of ALL. These findings suggest that associations of childhood leukemia and perinatal factors depend highly on subtype of leukemia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetics Home Reference: cytogenetically normal acute myeloid leukemia

Science.gov (United States)

... Testing (1 link) Genetic Testing Registry: Acute myeloid leukemia Other Diagnosis and Management Resources (3 links) Fred Hutchinson Cancer Research Center National Cancer Institute: Acute Myeloid Leukemia Treatment St. Jude Children's Research Hospital General Information ...

ViralORFeome: an integrated database to generate a versatile collection of viral ORFs.

Science.gov (United States)

Pellet, J; Tafforeau, L; Lucas-Hourani, M; Navratil, V; Meyniel, L; Achaz, G; Guironnet-Paquet, A; Aublin-Gex, A; Caignard, G; Cassonnet, P; Chaboud, A; Chantier, T; Deloire, A; Demeret, C; Le Breton, M; Neveu, G; Jacotot, L; Vaglio, P; Delmotte, S; Gautier, C; Combet, C; Deleage, G; Favre, M; Tangy, F; Jacob, Y; Andre, P; Lotteau, V; Rabourdin-Combe, C; Vidalain, P O

2010-01-01

Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.

UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication.

Directory of Open Access Journals (Sweden)

Peng-Nien Huang

2017-05-01

Full Text Available Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR in host cells. This study found that enterovirus A71 (EVA71 utilizes host UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1, a key endoplasmic reticulum protein (ER involved in UPR, to enhance viral replication and virulence. EVA71 forms replication complexes (RCs on cellular membranes that contain a mix of host and viral proteins to facilitate viral replication, but the components and processes involved in the assembly and function of RCs are not fully understood. Using EVA71 as a model, this study found that host UGGT1 and viral 3D polymerase co-precipitate along with other factors on membranous replication complexes to enhance viral replication. Increased UGGT1 levels elevated viral growth rates, while viral pathogenicity was observed to be lower in heterozygous knockout mice (Uggt1 +/- mice. These findings provide important insight on the role of UPR and host UGGT1 in regulating RNA virus replication and pathogenicity.

NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma.

Science.gov (United States)

Harhaj, Edward William; Giam, Chou-Zen

2018-05-03

The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4+ malignancy in 3-5% of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1 infected T cells. However, constitutive NF-κB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming NF-κB-induced senescence can selectively undergo clonal expansion after HTLV-1 infection. Tax expression is often silenced in the majority of ATLL due to genetic alterations in the tax gene or DNA hypermethylation of the 5'-LTR. Despite the loss of Tax, NF-κB activation remains persistently activated in ATLL due to somatic mutations in genes in the T/B-cell receptor (T/BCR) and NF-κB signaling pathways. In this review, we focus on the key events driving Tax-dependent and independent mechanisms of NF-κB activation during the multi-step process leading to ATLL. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

Science.gov (United States)

2017-08-18

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

Science.gov (United States)

Morales-Sánchez, A.; Pompa-Mera, E. N.; Fajardo-Gutiérrez, A.; Alvarez-Rodríguez, F. J.; Bekker-Méndez, V. C.; Flores-Chapa, J. de Diego; Flores-Lujano, J.; Jiménez-Hernández, E.; Peñaloza-González, J. G.; Rodríguez-Zepeda, M. C.; Torres-Nava, J. R.; Velázquez-Aviña, M. M.; Amador-Sánchez, R.; Alvarado-Ibarra, M.; Reyes-Zepeda, N.; Espinosa-Elizondo, R. M.; Pérez-Saldivar, M. L.; Núñez-Enríquez, J. C.; Mejía-Aranguré, J. M.; Fuentes-Pananá, E. M.

2014-01-01

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. PMID:25309913

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

Directory of Open Access Journals (Sweden)

Chou-Zen Giam

2016-06-01

Full Text Available HTLV-1 (Human T-cell lymphotropic virus type 1 is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ, encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8 and the ubiquitin E2 conjugating enzyme (UBC13—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

Science.gov (United States)

Giam, Chou-Zen; Semmes, Oliver John

2016-01-01

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

Heterogeneity in acute undifferentiated leukemia.

Science.gov (United States)

LeMaistre, A; Childs, C C; Hirsch-Ginsberg, C; Reuben, J; Cork, A; Trujillo, J M; Andersson, B; McCredie, K B; Freireich, E; Stass, S A

1988-01-01

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.

Viral Marketing

OpenAIRE

Sorina Raula Gîrboveanu; Silvia Puiu

2008-01-01

With consumers showing increasing resistance to traditional forms of advertising such as TV or newspaper ads, marketers have turned to alternate strategies, including viral marketing. Viral marketing exploits existing social networks by encouraging customers to share product information with their friends.In our study we are able to directly observe the effectiveness of person to person word of mouth advertising for hundreds of thousands of products for the first time

Esterase Isoenzyme Profiles in Acute and Chronic Leukemias.

Science.gov (United States)

Drexler, H G; Gignac, S M; Hoffbrand, A V; Minowada, J

1991-01-01

Using isoelectric focusing (IEF) a number of carboxylic esterase isoenzymes (EC 3.1.1.1) with isoelectric points between pH 4.5-8.0 can be separated. One particular isoenzyme with an isoelectric point at about pH 6.0, the Mono-band, can be selectively and completely inhibited by sodium fluoride; this isoenzyme comprises a number of closely related subcomponents and may appear in more than one band on the gel. We analyzed the expression of typical esterase isoenzyme patterns in cells from a large panel of leukemias which were tested under identical conditions by IEF on horizontal thin-layer polyacrylamide gels with an ampholyte of pH 2-11. The 442 cases of acute and chronic myeloid and lymphoid leukemia (AML/AMMoL, CML/CMML, ALL, CLL) were classified according to clinical, morpho-cytochemical and immunophenotyping criteria. While bands between pH 4.5-5.5 appeared not to be specific for lineage or stage of differentiation, isoenzymes between pH 6.6-7.7 provided information on the type of leukemia involved. Seven typical isoenzyme patterns termed Mono1/Mono2 (fo monocyte-associated), My1/My2 (myeloid), Lym1/Lym2 (lymphoid) and Und (undifferentiated) could be discerned. Lym and Und patterns are characterized by fewer bands with a weaker staining intensity than Mono and My patterns. Nearly all cases of lymphoid leukemias (acute and chronic) expressed only Lym or Und esterase isoenzyme patterns, but no Mono or My patterns. Cases of acute or chronic myeloid and (myelo)monocytic leukemia showed strong isoenzyme staining displaying predominantly Mono or My isoenzyme patterns. The isoenzyme patterns found in CML in lymphoid or myeloid blast crisis corresponded to those seen in the respective acute leukemias, ALL or AML. The Mono-band was found in most cases of leukemias with monocytic elements (AMMoL 80%, CML 44%, CMML 100%), in the occasional case of CML-myeloid blast crisis or AML, but in none of the cases of ALL or CLL. This isoenzyme is a distinctive, specific marker for

Survey of activated FLT3 signaling in leukemia.

Directory of Open Access Journals (Sweden)

Ting-lei Gu

Full Text Available Activating mutations of FMS-like tyrosine kinase-3 (FLT3 are found in approximately 30% of patients with acute myeloid leukemia (AML. FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3 and B cell acute lymphoblastic leukemia (normal and amplification of FLT3 cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC, we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.

Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Science.gov (United States)

2017-07-19

Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

Chronic lymphocytic leukemia cells are active participants in microenvironmental cross-talk

OpenAIRE

van Attekum, Martijn HA; Eldering, Eric; Kater, Arnon P

2017-01-01

The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenv...

Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features.

Science.gov (United States)

Reiffers, J; Bernard, P; Larrue, J; Dachary, D; David, B; Boisseau, M; Broustet, A

1985-01-01

This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.

HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases

Directory of Open Access Journals (Sweden)

Marco Baratella

2017-12-01

Full Text Available Human T cell leukemia virus type 1 (HTLV-1 is an oncogenic human retrovirus that has infected 10–15 million people worldwide. After a long latency, 3–5% of infected individuals will develop either a severe malignancy of CD4+ T cells, known as Adult T-cell Leukemia (ATL or a chronic and progressive inflammatory disease of the nervous system designated Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP. The precise mechanism behind HTLV-1 pathogenesis still remains elusive. Two viral regulatory proteins, Tax-1 and HTLV-1 bZIP factor (HBZ are thought to play a critical role in HTLV-1-associated diseases. Tax-1 is mainly involved in the onset of neoplastic transformation and in elicitation of the host’s inflammatory responses; its expression may be lost during cell clonal proliferation and oncogenesis. Conversely, HBZ remains constantly expressed in all patients with ATL, playing a role in the proliferation and maintenance of leukemic cells. Recent studies have shown that the subcellular distribution of HBZ protein differs in the two pathologies: it is nuclear with a speckled-like pattern in leukemic cells and is cytoplasmic in cells from HAM/TSP patients. Thus, HBZ expression and distribution could be critical in the progression of HTLV-1 infection versus the leukemic state or the inflammatory disease. Here, we reviewed recent findings on the role of HBZ in HTLV-1 related diseases, highlighting the new perspectives open by the possibility of studying the physiologic expression of endogenous protein in primary infected cells.

HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases.

Science.gov (United States)

Baratella, Marco; Forlani, Greta; Accolla, Roberto S

2017-01-01

Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus that has infected 10-15 million people worldwide. After a long latency, 3-5% of infected individuals will develop either a severe malignancy of CD4+ T cells, known as Adult T-cell Leukemia (ATL) or a chronic and progressive inflammatory disease of the nervous system designated Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP). The precise mechanism behind HTLV-1 pathogenesis still remains elusive. Two viral regulatory proteins, Tax-1 and HTLV-1 bZIP factor (HBZ) are thought to play a critical role in HTLV-1-associated diseases. Tax-1 is mainly involved in the onset of neoplastic transformation and in elicitation of the host's inflammatory responses; its expression may be lost during cell clonal proliferation and oncogenesis. Conversely, HBZ remains constantly expressed in all patients with ATL, playing a role in the proliferation and maintenance of leukemic cells. Recent studies have shown that the subcellular distribution of HBZ protein differs in the two pathologies: it is nuclear with a speckled-like pattern in leukemic cells and is cytoplasmic in cells from HAM/TSP patients. Thus, HBZ expression and distribution could be critical in the progression of HTLV-1 infection versus the leukemic state or the inflammatory disease. Here, we reviewed recent findings on the role of HBZ in HTLV-1 related diseases, highlighting the new perspectives open by the possibility of studying the physiologic expression of endogenous protein in primary infected cells.

Leukemia after radiotherapy for first primary cancers of various anatomic sites

International Nuclear Information System (INIS)

Boivin, J.F.; Hutchison, G.B.; Evans, F.B.; Abou-Daoud, K.T.; Junod, B.

1986-01-01

The authors conducted a case-control study designed to evaluate the association between radiotherapy for a first primary cancer and subsequent leukemia risk. Study subjects were selected from four tumor registries (California, Connecticut, Kansas, and Massachusetts). Cases were subjects with two primary concers; the second cancer was a leukemia diagnosed one year or more after the diagnosis of the first primary cancer. Control subjects were patients with single cancers. Two control subjects were chosen for each case matched for tumor registry, site of the first primary cancer, date of diagnosis of the first primary cancer, age, sex, and duration of survival after the first primary cancer. Separate analyses were carried out for chronic lymphatic leukemia (166 cases) and all other leukemias (232 cases). The relative risk of chronic lymphatic leukemia after radiotherapy was 0.7 and did not differ significantly from unity. For all other leukemias, relative risks were 1.6 after radiotherapy for first primary cancers of all sites, 2.4 after radiotherapy to trunk sites, 2.2 after radiotherapy for breast cancer, and 10.3 after radiotherapy for cancer of the corpus uteri. These relative risks for leukemias other than chronic lymphatic leukemia all differed significantly from unity

Diagnostic value of CD117 in differential diagnosis of acute leukemias.

Science.gov (United States)

Ahmadi, Abbas; Poorfathollah, Ali-Akbar; Aghaiipour, Mahnaz; Rezaei, Mansour; Nikoo-ghoftar, Mahin; Abdi, Mohammad; Gharib, Alireza; Amini, Amir

2014-07-01

C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in normal hematopoiesis. It has been demonstrated that its expression extremely increases in leukemias with myeloid commitment. We analyzed findings on CD117 expression together with other myeloid related markers in 203 de novo acute leukemias, referred to Iranian immunophenotyping centers: Iranian Blood Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were characterized based on the French American British cooperative group (FAB) and European Group for Immunological Classification of Leukemias (EGIL). The cases comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive was found (p = 0.036). The calculated specificity for myeloid involvement was 100 % for CD117 and CD33, and 98 % for CD13 and CD15 (p acute leukemias.

Trends in adult leukemia incidence and survival in Denmark, 1943-2003

DEFF Research Database (Denmark)

Thygesen, Lau Caspar; Nielsen, Ove Juul; Johansen, Christoffer

2009-01-01

The etiology of leukemia is largely unknown. Ecological data indicating trends in incidence and survival can provide information about changes in risk factors, can reflect underlying changes in diagnostic classification, and can measure therapeutic advances. From the records of the Danish Cancer...... Registry with registration starting from 1943, we calculated age-specific, period-specific, and age-standardized (world standard) incidence rates of chronic lymphoid leukemia (CLL), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML) for persons above the age...... of 18. Kaplan-Meier survival curves and median survival times were calculated. Between 1943 and 2003, there were 26,036 cases of leukemia reported. The age-specific incidence rates of CLL, CML, and AML were higher for older men and women, while the incidence rates of ALL by age were more homogeneous...

Hairy Cell Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Hairy cell leukemia treatment options include watchful waiting when there are no symptoms, chemotherapy, biologic therapy, surgery, and targeted therapy. Learn more about the diagnosis and treatment of newly diagnosed and recurrent hairy cell leukemia in this expert-reviewed summary.

Trends in incidence of leukemia in Poland after the Chernobyl disaster

International Nuclear Information System (INIS)

Kwiatkowski, B.

1996-01-01

After the Chernobyl accident the whole population of Poland was exposed to low-level radiation mainly emitted by I-131 and Cs-137. In 6-year period the incidence of leukemia increased in 2 groups of children: age 0-4 in males and 5-7 in females. In adults in some clinical types of leukemia significant trends of incidence were observed: in acute myleoid leukemia in age groups of 70-79 for males, in chronic myleoid leukemia in age groups of 40-49 and 60-69 for females, in chronic lymphatic leukemia in age group of 70-79 for males. Non of those trends was significant prior to the Chernobyl disaster

Value of Sharing: Viral Advertisement

OpenAIRE

Duygu Aydın; Aşina Gülerarslan; Süleyman Karaçor; Tarık Doğan

2013-01-01

Sharing motivations of viral advertisements by consumers and the impacts of these advertisements on the perceptions for brand will be questioned in this study. Three fundamental questions are answered in the study. These are advertisement watching and sharing motivations of individuals, criteria of liking viral advertisement and the impact of individual attitudes for viral advertisement on brand perception respectively. This study will be carried out via a viral advertise...

Viral Marketing and Academic Institution

OpenAIRE

Koktová, Silvie

2010-01-01

This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

Acute leukemia classification by ensemble particle swarm model selection.

Science.gov (United States)

Escalante, Hugo Jair; Montes-y-Gómez, Manuel; González, Jesús A; Gómez-Gil, Pilar; Altamirano, Leopoldo; Reyes, Carlos A; Reta, Carolina; Rosales, Alejandro

2012-07-01

Acute leukemia is a malignant disease that affects a large proportion of the world population. Different types and subtypes of acute leukemia require different treatments. In order to assign the correct treatment, a physician must identify the leukemia type or subtype. Advanced and precise methods are available for identifying leukemia types, but they are very expensive and not available in most hospitals in developing countries. Thus, alternative methods have been proposed. An option explored in this paper is based on the morphological properties of bone marrow images, where features are extracted from medical images and standard machine learning techniques are used to build leukemia type classifiers. This paper studies the use of ensemble particle swarm model selection (EPSMS), which is an automated tool for the selection of classification models, in the context of acute leukemia classification. EPSMS is the application of particle swarm optimization to the exploration of the search space of ensembles that can be formed by heterogeneous classification models in a machine learning toolbox. EPSMS does not require prior domain knowledge and it is able to select highly accurate classification models without user intervention. Furthermore, specific models can be used for different classification tasks. We report experimental results for acute leukemia classification with real data and show that EPSMS outperformed the best results obtained using manually designed classifiers with the same data. The highest performance using EPSMS was of 97.68% for two-type classification problems and of 94.21% for more than two types problems. To the best of our knowledge, these are the best results reported for this data set. Compared with previous studies, these improvements were consistent among different type/subtype classification tasks, different features extracted from images, and different feature extraction regions. The performance improvements were statistically significant

Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

Science.gov (United States)

2018-02-16

Profoosionaf 7 ,0 Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia Brittany Lenz, MD, Arturo Dominguez, MD, Adnan Mir, MD, PhD Objectives...with pre-B cell acute lymphoblastic leukemia was admitted for presumed septic shock secondary to an unknown infectious etiology. The patient was...NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD

Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

Science.gov (United States)

2016-05-13

Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Science.gov (United States)

2013-06-04

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Identification of viral infections in the prostate and evaluation of their association with cancer

Directory of Open Access Journals (Sweden)

Calderon-Cardenas German

2010-06-01

Full Text Available Abstract Background Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs, and human cytomegalovirus (HCMV infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV was identified in prostate tissue with a high prevalence observed in prostate cancer (PC patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q. Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. Methods 130 subjects (55 prostate cancer cases and 75 controls were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. Results R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0% cases and 4 (5.3% controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027 by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. Conclusions We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

[Emergent viral infections

NARCIS (Netherlands)

Galama, J.M.D.

2001-01-01

The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic

Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.

Science.gov (United States)

Horton, Terzah M; Gannavarapu, Anurhadha; Blaney, Susan M; D'Argenio, David Z; Plon, Sharon E; Berg, Stacey L

2006-07-01

Although there is effective chemotherapy for many patients with leukemia, 20% of children and up to 65% of adults relapse. Novel therapies are needed to treat these patients. Leukemia cells are very sensitive to the proteasome inhibitor bortezomib (VELCADE(R), PS-341), which enhances the in vitro cytotoxic effects of dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib enhances the cytotoxicity of agents used in leukemia, we employed an in vitro tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin, cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor HA14.1. We demonstrated that primary leukemia lymphoblasts and leukemia cell lines are sensitive to bortezomib, with an average IC(50) of 12 nM. Qualitative and quantitative bortezomib-drug interactions were evaluated using the universal response surface approach (URSA). Bortezomib was synergistic with dexamethasone in dexamethasone-sensitive leukemia cells, and additive with vincristine, asparaginase, cytarabine, and doxorubicin. The anti-leukemic activity of bortezomib was also additive with geldanamycin and HA14.1, and additive or synergistic with trichostatin A. These results were compared to analysis using the median-dose effect method, which generated complex drug interactions due to differences in dose-response curve sigmoidicities. These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia.

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

International Nuclear Information System (INIS)

Ding, Kai; Wang, Xiao-ming; Fu, Rong; Ruan, Er-bao; Liu, Hui; Shao, Zong-hong

2012-01-01

To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M 3 , 33.3% in M 2 , and 28.6% in M 5 . Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype, but not with age, gender, white blood count or percentage of blast cells. The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia

The MLL recombinome of acute leukemias in 2017

NARCIS (Netherlands)

C. Meyer; T. Burmeister; D. Gröger (D.); G. Tsaur; L. Fechina; A. Renneville; R. Sutton; N. Venn; M. Emerenciano (M.); Pombo-De-Oliveira, M.S. (M. S.); Barbieri Blunck, C. (C.); Almeida Lopes, B. (B.); J. Zuna; J. Trka (Jan); Ballerini, P. (P.); Lapillonne, H. (H.); E. de Braekeleer; G. Cazzaniga (Gianni); Corral Abascal, L. (L.); V.H.J. van der Velden (Vincent); E. Delabesse; Park, T.S. (T. S.); S.H. Oh (S.); M.L.M. Silva (M. L M); T. Lund-Aho (T.); V. Juvonen (V.); A.S. Moore (A.); O. Heidenreich; Vormoor, J. (J.); Zerkalenkova, E. (E.); Olshanskaya, Y. (Y.); Bueno, C. (C.); P. Menéndez (Pablo); A. Teigler-Schlegel; U. zur Stadt; Lentes, J. (J.); G. Göhring (Gudrun); Kustanovich, A. (A.); O. Aleinikova (O.); Schäfer, B.W. (B. W.); S. Kubetzko (S.); H.O. Madsen; Gruhn, B. (B.); Duarte, X. (X.); P. Gameiro; E. Lippert (Eric); Bidet, A. (A.); J.-M. Cayuela (Jean-Michel); E. Clappier; C.N. Alonso (Cristina); C.M. Zwaan (Christian Michel); M.M. van den Heuvel-Eibrink (Marry); S. Izraeli (Shai); L. Trakhtenbrot; P. Archer (P.); J. Hancock; A. Möricke; Alten, J. (J.); M. Schrappe (Martin); M. Stanulla (Martin); S. Strehl; A. Attarbaschi (Andishe); M.N. Dworzak (Michael); Haas, O.A. (O. A.); R. Panzer-Grümayer (Renate); L. Sedek (Lukasz); Szczepa, T. (T.); A. Caye (Aurélie); Suarez, L. (L.); H. Cavé (Helene); R. Marschalek (Rolf)

2018-01-01

textabstractChromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner

High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

Science.gov (United States)

2018-02-28

Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

Czech Academy of Sciences Publication Activity Database

Kanderová, V.; Kuzilkova, D.; Stuchlý, J.; Vašková, M.; Brdička, Tomáš; Fišer, K.; Hrušák, O.; Lund-Johansen, F.; Kalina, T.

2016-01-01

Roč. 15, č. 4 (2016), s. 1246-1261 ISSN 1535-9476 R&D Projects: GA MŠk 2B06064 Institutional support: RVO:68378050 Keywords : acute lymphoblastic-leukemia * acute promyelocytic leukemia * cytometric immunobead assay * caspase-dependent cleavage * acute myeloid-leukemia * gene-expression * fusion proteins * flow-cytometry * pcr data * b-cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.540, year: 2016

Identification of a High Affinity Nucleocapsid Protein Binding Element from The Bovine Leukemia Virus Genome

Science.gov (United States)

Yildiz, F. Zehra; Babalola, Kathleen; Summers, Michael F.

2012-01-01

Retroviral genome recognition is mediated by interactions between the nucleocapsid (NC) domain of the virally encoded Gag polyprotein and cognate RNA packaging elements that, for most retroviruses, appear to reside primarily within the 5′-untranslated region (5′-UTR) of the genome. Recent studies suggest that a major packaging determinant of Bovine Leukemia Virus (BLV), a member of the human T-cell leukemia virus (HTLV)/BLV family and a non-primate animal model for HTLV-induced leukemogenesis, resides within the gag open reading frame. We have prepared and purified the recombinant BLV NC protein and conducted electrophoretic mobility shift and isothermal titration calorimetry studies with RNA fragments corresponding to these proposed packaging elements. The gag-derived RNAs did not exhibit significant affinity for NC, suggesting an alternate role in packaging. However, an 83-nucleotide fragment of the 5′-UTR that resides just upstream of the gag start codon binds NC stoichiometrically and with high affinity (Kd = 136 ± 21 nM). These nucleotides were predicted to form tandem hairpin structures, and studies with smaller fragments indicate that the NC binding site resides exclusively within the distal hairpin (residues G369- U399, Kd = 67 ± 8 nM at physiological ionic strength). Unlike all other structurally characterized retroviral NC binding RNAs, this fragment is not expected to contain exposed guanosines, suggesting that RNA binding may be mediated by a previously uncharacterized mechanism. PMID:22846919

Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity

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Aboud Mordechai

2004-08-01

Full Text Available Abstract HTLV-1 is the etiological agent of adult T-cell leukemia (ATL, the neurological syndrome TSP/HAM and certain other clinical disorders. The viral Tax protein is considered to play a central role in the process leading to ATL. Tax modulates the expression of many viral and cellular genes through the CREB/ATF-, SRF- and NF-κB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process. Together, these capacities render Tax highly oncogenic as reflected by its ability to transform rodent fibroblasts and primary human T-cells and to induce tumors in transgenic mice. In this article we discuss these effects of Tax and their apparent contribution to the HTLV-1 associated leukemogenic process. Notably, however, shortly after infection the virus enters into a latent state, in which viral gene expression is low in most of the HTLV-1 carriers' infected T-cells and so is the level of Tax protein, although rare infected cells may still display high viral RNA. This low Tax level is evidently insufficient for exerting its multiple oncogenic effects. Therefore, we propose that the latent virus must be activated, at least temporarily, in order to elevate Tax to its effective level and that during this transient activation state the infected cells may acquire some oncogenic mutations which can enable them to

Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity.

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Azran, Inbal; Schavinsky-Khrapunsky, Yana; Aboud, Mordechai

2004-08-13

HTLV-1 is the etiological agent of adult T-cell leukemia (ATL), the neurological syndrome TSP/HAM and certain other clinical disorders. The viral Tax protein is considered to play a central role in the process leading to ATL. Tax modulates the expression of many viral and cellular genes through the CREB/ATF-, SRF- and NF-kappaB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process. Together, these capacities render Tax highly oncogenic as reflected by its ability to transform rodent fibroblasts and primary human T-cells and to induce tumors in transgenic mice. In this article we discuss these effects of Tax and their apparent contribution to the HTLV-1 associated leukemogenic process. Notably, however, shortly after infection the virus enters into a latent state, in which viral gene expression is low in most of the HTLV-1 carriers' infected T-cells and so is the level of Tax protein, although rare infected cells may still display high viral RNA. This low Tax level is evidently insufficient for exerting its multiple oncogenic effects. Therefore, we propose that the latent virus must be activated, at least temporarily, in order to elevate Tax to its effective level and that during this transient activation state the infected cells may acquire some oncogenic mutations which can enable them to further progress towards

A typical presentation of acute myeloid leukemia

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Udayakumar N

2006-01-01

Full Text Available A young man who presented with fever, altered sensorium and sudden onset tachypnea, is described. Arterial blood gas analysis, revealed the presence of severe high anion gap metabolic acidosis, with compensatory respiratory alkalosis and normal oxygen saturation. A detailed neurological, nephrological, biochemical and hematological evaluation, revealed the presence of Acute myeloid leukemia, with lactic acidosis and hyponatremia. There are very few reports of presentation of leukemia as lactic acidosis. This case report highlights the need for emergency room physicians, to consider the possibility of lactic acidosis, as one of the causes of high anion gap acidosis and to meticulously investigate the cause of lactic acidosis. We describe a rare clinical instance of lactic acidosis as the presenting manifestation of Acute myeloid leukemia.

Leukemias in the progeny of exposed parents

International Nuclear Information System (INIS)

Kosenko, M.M.; Gudkova, N.V.

1996-01-01

The purpose of this study was to assess the incidence of leukemias among the progeny of exposed parents. The parents were exposed as a result of discharge of radioactive waste from the Mayak atomic plant into the Techa river in the Southern Urals. The doses per parents gonads, ranging from 0.035 to 1.27 Sv, were due to external exposure in 1950-1956 and to incorporation of Cs-137. Nine cases with leukemia and four with lympohoma were recorded in 13.500 antenatally exposed subjects and descendants of exposed parents over the period of 1950 to 1988. The leukemia morbidity index for the progeny of exposed parents was 2.51, which virtually not statistically differ from that in control group. Refs. 7, figs. 3, tabs. 3

Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region

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Murohashi, Ikuo

1985-01-01

A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (95 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 women-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia (2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)). Based on rates for the general population, 0.45 case would be expected, and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 11.77 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region. (author).

Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region

International Nuclear Information System (INIS)

Murohashi, Ikuo

1985-01-01

A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (95 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 women-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia [2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)]. Based on rates for the general population, 0.45 case would be expected, and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 11.77 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region. (author)

Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Science.gov (United States)

2017-06-27

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Distinction of leukemia patients' and healthy persons' serum using FTIR spectroscopy

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Sheng, Daping; Liu, Xingcun; Li, Weizu; Wang, Yuchan; Chen, Xianliang; Wang, Xin

2013-01-01

In this paper, FTIR spectroscopy was applied to compare the serum from leukemia patients with the serum from healthy persons. IR spectra of leukemia patients' serum were similar with IR spectra of healthy persons' serum, and they were all made up of proteins, lipids and nucleic acids, etc. In order to identify leukemia patients' serum and healthy persons' serum, the H1075/H1542, H1045/H1467, H2959/H2931 ratios were measured. The H2959/H2931 ratio had the highest significant difference among these ratios and might be a useful factor for identifying leukemia patients' serum and healthy persons' serum. Furthermore, from curve fitting, the RNA/DNA (A1115/A1028) ratios were observed to be lower in leukemia patients' serum than those in healthy persons' serum. The results indicated FTIR spectroscopic study of serum might be a useful tool in the field of leukemia research and diagnosis.

Retroviral DNA--the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats.

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Nesina, Stefanie; Katrin Helfer-Hungerbuehler, A; Riond, Barbara; Boretti, Felicitas S; Willi, Barbara; Meli, Marina L; Grest, Paula; Hofmann-Lehmann, Regina

2015-12-21

The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for

MYC as therapeutic target in leukemia and lymphoma

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Cortiguera MG

2015-07-01

Full Text Available Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC, CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla, 3Department of Molecular Biology, University of Cantabria, Santander, Spain Abstract: MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma, amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC–MAX interaction impair MYC-mediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC–MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC

Mast cell leukemia associated with undefined morphology and chronic basophilic leukemia.

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Cehreli, Cavit; Alacacioglu, Inci; Piskin, Ozden; Ates, Halil; Cehreli, Ruksan; Calibasi, Gizem; Yuksel, Erdinc; Ozkal, Sermin; Ozsan, Guner H

2014-01-01

Mast cell leukemia (MCL) is rare type of neoplasia with an incidence of 1% in a large series of 342 adult patients with systemic mastocytosis (SM). Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia with appearance of 7 cases in the literature. A 73 year-old female patient who presented with weaknes, had a prolonged duration of hematologic remission after treatment of her CBL by hydroxyurea (HU). Evolution of SM occurring as a second neoplasia concurrently with relapse of de novo CBL was demonstrated by mast cells (MCs) infiltration in the bone marrow (BM) biopsy and smear and increase in tryptase level. Transformation to MCL with simultaneous occurrance of accelerated phase of CBL were documented by the appearance of MCs in both BM and peripheral blood (PB) smears, antigen expressions detected by flow cytometry and spesific stains. Sequence analysis of c-kit gene revealed c-kit exon 11 K550N mutation. Undefined associations of MCL with different mast cell morphology, increase in IL-6 level and accelerated phase of de novo CBL was described. Elevations in CRP and IL-6 levels occurring with increases in basophil counts to high levels revealed that febrile episodes with abdominal pain seen in our patient were induced by increase in IL-6 levels released from neoplastic basophils. Neoplastic basophils with diffuse and coarse basophilic granules possibly mimic neutrophils with toxic granules and cause wrong characterization of neoplastic basophils as neutrophils by the automated blood cell counters and misleaded physicians.

Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

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Rodriguez-Rodriguez, Sergio; Pomerantz, Alan; Demichelis-Gomez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benitez, Olga; Aguayo-Gonzalez, Alvaro

2016-01-01

The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

Hairy Cell Leukemia Treatment (PDQ®)—Health Professional Version

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Hairy cell leukemia treatment options include surveillance, chemotherapy, targeted therapy/immunotherapy, and splenectomy. The decision to treat is based on cytopenias, splenomegaly, or infectious complications. Get detailed information about hairy cell leukemia in this clinician summary.

The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax.

Science.gov (United States)

Mann, Melanie C; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K

2014-09-01

The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Juvenile myelomonocytic leukemia presenting as bilateral breast masses

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Edison, Michele N.; Letter, Haley P. [Florida Hospital, Department of Radiology, Orlando, FL (United States); University of Central Florida, College of Medicine, Orlando, FL (United States); O' Dell, M.C. [University of Central Florida, College of Medicine, Orlando, FL (United States); Children' s Hospital of Philadelphia, Pediatric Radiology, Philadelphia, PA (United States); Scherer, Kurt; Williams, Jennifer L. [Florida Hospital, Department of Radiology, Orlando, FL (United States); University of Central Florida, College of Medicine, Orlando, FL (United States); Florida State University, College of Medicine, Tallahassee, FL (United States)

2017-01-15

An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia. The authors hope that increased reporting and research regarding pediatric breast masses will help create awareness for such cases. (orig.)

Juvenile myelomonocytic leukemia presenting as bilateral breast masses

International Nuclear Information System (INIS)

Edison, Michele N.; Letter, Haley P.; O'Dell, M.C.; Scherer, Kurt; Williams, Jennifer L.

2017-01-01

An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia. The authors hope that increased reporting and research regarding pediatric breast masses will help create awareness for such cases. (orig.)

HOXA9 is required for survival in human MLL-rearranged acute leukemias

NARCIS (Netherlands)

J. Faber (Joerg); A.V. Krivtsov (Andrei); M.C. Stubbs (Matthew); R. Wright (Renee); T.N. Davis (Tina); M.M. van den Heuvel-Eibrink (Marry); C.M. Zwaan (Christian Michel); A.L. Kung (Andrew); S.A. Armstrong (Scott)

2009-01-01

textabstractLeukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biologic characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression

An approach for leukemia classification based on cooperative game theory.

Science.gov (United States)

Torkaman, Atefeh; Charkari, Nasrollah Moghaddam; Aghaeipour, Mahnaz

2011-01-01

Hematological malignancies are the types of cancer that affect blood, bone marrow and lymph nodes. As these tissues are naturally connected through the immune system, a disease affecting one of them will often affect the others as well. The hematological malignancies include; Leukemia, Lymphoma, Multiple myeloma. Among them, leukemia is a serious malignancy that starts in blood tissues especially the bone marrow, where the blood is made. Researches show, leukemia is one of the common cancers in the world. So, the emphasis on diagnostic techniques and best treatments would be able to provide better prognosis and survival for patients. In this paper, an automatic diagnosis recommender system for classifying leukemia based on cooperative game is presented. Through out this research, we analyze the flow cytometry data toward the classification of leukemia into eight classes. We work on real data set from different types of leukemia that have been collected at Iran Blood Transfusion Organization (IBTO). Generally, the data set contains 400 samples taken from human leukemic bone marrow. This study deals with cooperative game used for classification according to different weights assigned to the markers. The proposed method is versatile as there are no constraints to what the input or output represent. This means that it can be used to classify a population according to their contributions. In other words, it applies equally to other groups of data. The experimental results show the accuracy rate of 93.12%, for classification and compared to decision tree (C4.5) with (90.16%) in accuracy. The result demonstrates that cooperative game is very promising to be used directly for classification of leukemia as a part of Active Medical decision support system for interpretation of flow cytometry readout. This system could assist clinical hematologists to properly recognize different kinds of leukemia by preparing suggestions and this could improve the treatment of leukemic

Radioisotope examination of hairy-cell leukemia patients

International Nuclear Information System (INIS)

Fortynova, J.; Friedmann, B.; Bakos, K.; Malaskova, V.; Voslarova, Z.; Vopatova, M.

1983-01-01

13 patients with hairy-cell leukemia were simultaneously tested using different radioisotope methods (scintiscan of the spleen and bone marrow, total blood volume and erythrocytic pool in the spleen, erythrocyte and platelet kinetics). Some of the methods (bone marrow scintiscan, total blood volume and erythrocytic pool in the spleen, and kinetic studies) produced characteristic results in those patients: they could add precision to the diagnosis of the disease, and they could also be used for better elucidation of the pathogenic mechanisms of other clinical signs characteristic of hairy-cell leukemia. In spite of the undeniably significant value of the said methods for precise diagnosis of hairy-cell leukemia, histological tests of the bioptic material of bone marrow and spleen and bone marrow needle biopsy remain better and indispensable methods. (author)

The MLL recombinome of acute leukemias in 2013

Science.gov (United States)

Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

2013-01-01

Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements. PMID:23628958

Transfer of ERR for radiation-related leukemia from Japanese population to Chinese population

International Nuclear Information System (INIS)

Huang Liqiong; Sun Zhijuan; Zhao Yongcheng; Wang Jixian

2011-01-01

Objective: To establish a transfer model for excess relative risk (ERR) for radiation-related leukemia from Japanese population to Chinese population. Methods: Combined ERR of several subtypes of leukemia published in 1994, with the corresponding leukemia baseline incidence rates obtained from Cancer Incidence in Five Continents Vol. Ⅸ (CI5-Ⅸ) for Japanese population and Chinese population, a weighted risk transfer model was employed between an additive model and a multiplicative model, to execute ERR transfer. Results: A range of weighing factors was proposed for risk transfer models: weighing factor was 0.4 for male and 0.3 for female, acute lymphoblastic leukemia, acute myeloid leukemia and chronic myeloid leukemia. The uncertainty for ERR transfer was characterized by lognormal distribution. Conclusions: Based on the difference of baseline incidence rate for subtypes of leukemia between Japanese population and Chinese population, the transfer model and these weighing factors discussed in the present study could be applicable to transfer ERR for radiation-related leukemia from Japanese population to Chinese population. (authors)

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

Science.gov (United States)

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Laboratory procedures to generate viral metagenomes.

Science.gov (United States)

Thurber, Rebecca V; Haynes, Matthew; Breitbart, Mya; Wegley, Linda; Rohwer, Forest

2009-01-01

This collection of laboratory protocols describes the steps to collect viruses from various samples with the specific aim of generating viral metagenome sequence libraries (viromes). Viral metagenomics, the study of uncultured viral nucleic acid sequences from different biomes, relies on several concentration, purification, extraction, sequencing and heuristic bioinformatic methods. No single technique can provide an all-inclusive approach, and therefore the protocols presented here will be discussed in terms of hypothetical projects. However, care must be taken to individualize each step depending on the source and type of viral-particles. This protocol is a description of the processes we have successfully used to: (i) concentrate viral particles from various types of samples, (ii) eliminate contaminating cells and free nucleic acids and (iii) extract, amplify and purify viral nucleic acids. Overall, a sample can be processed to isolate viral nucleic acids suitable for high-throughput sequencing in approximately 1 week.

Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

Directory of Open Access Journals (Sweden)

Eliana C.A. Benites

2014-07-01

Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

Hepatitis A through E (Viral Hepatitis)

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... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

Acute lymphoblastic leukemia (ALL)

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... better. Most children with ALL can be cured. Children often have a better outcome than adults. ... Both leukemia itself and the treatment can lead to many problems such as bleeding, weight loss, and infections.

Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

Science.gov (United States)

Chung, Clement; Ma, Hilary

2017-09-01

Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia. Evidence indicates that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up-front induction therapy. Core-binding factor acute myeloid leukemia in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer. © 2017 Pharmacotherapy Publications

Imatinib mesylate in chronic myelogenous leukemia: a Congolese ...

African Journals Online (AJOL)

Major cytogenetic response was noticed in 87.18%. After a median follow up of 12 months, chronic myeloid leukemia had not progressed to the accelerated or blastic phase in an estimated 91.8% of patients and 86.6% were alive. Conclusion: Imatinib is effective in newly chronic phase chronic myeloid leukemia patient ...

Leukemia & Lymphoma Society

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... be the exclusive property of The Leukemia & Lymphoma Society which in its sole discretion may use this material as it sees fit. I agree to the terms of the Standard Photography Release.* Submit * This field is required * Please fix the validation error messages in the Form Your story was ...

JAK inhibitors suppress t(8;21) fusion protein-induced leukemia

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Lo, Miao-Chia; Peterson, Luke F.; Yan, Ming; Cong, Xiuli; Hickman, Justin H.; DeKelver, Russel C.; Niewerth, Denise; Zhang, Dong-Er

2014-01-01

Oncogenic mutations in components of the JAK/STAT pathway, including those in cytokine receptors and JAKs, lead to increased activity of downstream signaling and are frequently found in leukemia and other hematological disorders. Thus, small-molecule inhibitors of this pathway have been the focus of targeted therapy in these hematological diseases. We previously showed that t(8;21) fusion protein AML1-ETO and its alternatively spliced variant AML1-ETO9a (AE9a) enhance the JAK/STAT pathway via down-regulation of CD45, a negative regulator of this pathway. To investigate the therapeutic potential of targeting JAK/STAT in t(8;21) leukemia, we examined the effects of a JAK2-selective inhibitor TG101209 and a JAK1/2-selective inhibitor INCB18424 on t(8;21) leukemia cells. TG101209 and INCB18424 inhibited proliferation and promoted apoptosis of these cells. Furthermore, TG101209 treatment in AE9a leukemia mice reduced tumor burden and significantly prolonged survival. TG101209 also significantly impaired the leukemia-initiating potential of AE9a leukemia cells in secondary recipient mice. These results demonstrate the potential therapeutic efficacy of JAK inhibitors in treating t(8;21) AML. PMID:23812420

Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

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Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

2016-07-01

Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.

Differentiation Therapy of Acute Myeloid Leukemia

International Nuclear Information System (INIS)

Gocek, Elzbieta; Marcinkowska, Ewa

2011-01-01

Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D 3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML

Differentiation Therapy of Acute Myeloid Leukemia

Energy Technology Data Exchange (ETDEWEB)

Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

2011-05-16

Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

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Zuurbier, Linda; Gutierrez, Alejandro; Mullighan, Charles G.; Canté-Barrett, Kirsten; Gevaert, A. Olivier; de Rooi, Johan; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G.C.A.M.; Sonneveld, Edwin; Look, A. Thomas; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2014-01-01

Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. PMID:23975177

Faktor Risiko Non Viral Pada Karsinoma Nasofaring

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Sukri Rahman

2015-09-01

Full Text Available Abstrak           Latar belakang: Karsinoma nasofaring adalah tumor ganas epitel nasofaring yang sampai saat ini penyebabnya belum diketahui, infeksi virus Epstein Barr dilaporkan sebagai faktor dominan terjadinya karsinoma nasofaring tetapi faktor non viral juga berperan untuk timbulnya keganasan nasofaring. Tujuan: Untuk mengetahui faktor non viral  yang dapat meningkatkan kejadian karsinoma nasofaring sehingga dapat mencegah dan menghindari faktor-faktor non viral tersebut. Tinjauan Pustaka: Karsinoma nasofaring merupakan tumor ganas epitel nasofaring yang penyebabnya berhubungan dengan faktor viral dan non viral diantaranya asap rokok, ikan asin, formaldehid, genetik, asap kayu bakar , debu kayu, infeksi kronik telinga hidung tenggorok, alkohol dan obat tradisional. Kesimpulan: Pembuktian secara klinis dan ilmiah terhadap faktor non viral sebagai penyebab timbulnya karsinoma nasofaring masih belum dapat dijelaskan secara pasti. Faktor non viral merupakan salah satu faktor risiko yang dapat meningkatkan angka kejadian timbulnya keganasan nasofaring Kata kunci: karsinoma nasofaring, faktor risiko, non viral AbstractBackground: Nasopharyngeal carcinoma is a malignant epithelial nasopharyngeal tumor that until now the cause still unknown, Epstein barr virus infection had reported as predominant occurance of nasopharyngeal carcinoma but non viral factors may also contribute to the onset of the incidence of nasopharyngeal malignancy. Purpose: To find non viral factors that may increase the incidence of nasopharyngel carcinoma in order to prevent and avoid non-viral factors Literature: Nasopharyngeal carcinoma is a malignant tumor that causes nasopharyngeal epithelium associated with viral and non-viral factors such as cigarette smoke, salt fish, formaldehyde, genetic, wood smoke ,wood dust, ear nose throat chronic infections, alcohol, and traditional medicine. Conclusion: Clinically and scientifically proving the non-viral factors as

Osseous pseudo-myelomatose compromise, in leukemia chronic lymphoid

International Nuclear Information System (INIS)

Martinez Betancur, Octavio; Lopez de Goenaga, Maria Ines

2000-01-01

It was described a case of chronic lymphocytic leukemia in a 75 year old man, with pseudomyelomatosis osteolytic lesions in the skull, excluding other potential causes of osteolytic lesions in the clinical context of malignant lymphoproliferative neoplasm. The real frequency of osseous compromise in chronic lymphocytic leukemia is 10%. Lesions are defined as generalized osteoporosis and osteolysis with lacunar aspect, similar to myeloma lesions. Because histopathology in lymphoproliferative neoplasms may be similar, it might be difficult to diagnose chronic lymphocytic leukemia certainly, if the clinical manifestations are not considered. Differential diagnosis with other lymphoproliferative neoplasm is based basically in absolute lymphocytosis greater than 10 X 109/L, with lymphocytes with mature appearance

Metabolism goes viral.

Science.gov (United States)

Miyake-Stoner, Shigeki J; O'Shea, Clodagh C

2014-04-01

Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.

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Mathew, Nimitha R; Baumgartner, Francis; Braun, Lukas; O'Sullivan, David; Thomas, Simone; Waterhouse, Miguel; Müller, Tony A; Hanke, Kathrin; Taromi, Sanaz; Apostolova, Petya; Illert, Anna L; Melchinger, Wolfgang; Duquesne, Sandra; Schmitt-Graeff, Annette; Osswald, Lena; Yan, Kai-Li; Weber, Arnim; Tugues, Sonia; Spath, Sabine; Pfeifer, Dietmar; Follo, Marie; Claus, Rainer; Lübbert, Michael; Rummelt, Christoph; Bertz, Hartmut; Wäsch, Ralph; Haag, Johanna; Schmidts, Andrea; Schultheiss, Michael; Bettinger, Dominik; Thimme, Robert; Ullrich, Evelyn; Tanriver, Yakup; Vuong, Giang Lam; Arnold, Renate; Hemmati, Philipp; Wolf, Dominik; Ditschkowski, Markus; Jilg, Cordula; Wilhelm, Konrad; Leiber, Christian; Gerull, Sabine; Halter, Jörg; Lengerke, Claudia; Pabst, Thomas; Schroeder, Thomas; Kobbe, Guido; Rösler, Wolf; Doostkam, Soroush; Meckel, Stephan; Stabla, Kathleen; Metzelder, Stephan K; Halbach, Sebastian; Brummer, Tilman; Hu, Zehan; Dengjel, Joern; Hackanson, Björn; Schmid, Christoph; Holtick, Udo; Scheid, Christof; Spyridonidis, Alexandros; Stölzel, Friedrich; Ordemann, Rainer; Müller, Lutz P; Sicre-de-Fontbrune, Flore; Ihorst, Gabriele; Kuball, Jürgen; Ehlert, Jan E; Feger, Daniel; Wagner, Eva-Maria; Cahn, Jean-Yves; Schnell, Jacqueline; Kuchenbauer, Florian; Bunjes, Donald; Chakraverty, Ronjon; Richardson, Simon; Gill, Saar; Kröger, Nicolaus; Ayuk, Francis; Vago, Luca; Ciceri, Fabio; Müller, Antonia M; Kondo, Takeshi; Teshima, Takanori; Klaeger, Susan; Kuster, Bernhard; Kim, Dennis Dong Hwan; Weisdorf, Daniel; van der Velden, Walter; Dörfel, Daniela; Bethge, Wolfgang; Hilgendorf, Inken; Hochhaus, Andreas; Andrieux, Geoffroy; Börries, Melanie; Busch, Hauke; Magenau, John; Reddy, Pavan; Labopin, Myriam; Antin, Joseph H; Henden, Andrea S; Hill, Geoffrey R; Kennedy, Glen A; Bar, Merav; Sarma, Anita; McLornan, Donal; Mufti, Ghulam; Oran, Betul; Rezvani, Katayoun; Shah, Omid; Negrin, Robert S; Nagler, Arnon; Prinz, Marco; Burchert, Andreas; Neubauer, Andreas; Beelen, Dietrich; Mackensen, Andreas; von Bubnoff, Nikolas; Herr, Wolfgang; Becher, Burkhard; Socié, Gerard; Caligiuri, Michael A; Ruggiero, Eliana; Bonini, Chiara; Häcker, Georg; Duyster, Justus; Finke, Jürgen; Pearce, Erika; Blazar, Bruce R; Zeiser, Robert

2018-03-01

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD + leukemia cells. This synergized with the allogeneic CD8 + T cell response, leading to long-term survival in six mouse models of FLT3-ITD + AML. Sorafenib-related IL-15 production caused an increase in CD8 + CD107a + IFN-γ + T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD + AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8 + T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors: 1950 – 2001

Science.gov (United States)

Hsu, Wan-Ling; Preston, Dale L.; Soda, Midori; Sugiyama, Hiromi; Funamoto, Sachiyo; Kodama, Kazunori; Kimura, Akiro; Kamada, Nanao; Dohy, Hiroo; Tomonaga, Masao; Iwanaga, Masako; Miyazaki, Yasushi; Cullings, Harry M.; Suyama, Akihiko; Ozasa, Kotaro; Shore, Roy E.; Mabuchi, Kiyohiko

2013-01-01

A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This paper presents analyses of radiation effects on leukemia, lymphoma, and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry-based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma, and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose response relationship and, to the extent the data allowed, to investigate variation in the excess risks with sex, attained age, exposure age, and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a non-linear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this non-linearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence

Cytosine Arabinoside Influx and Nucleoside Transport Sites in Acute Leukemia

OpenAIRE

Wiley, J. S.; Jones, S. P.; Sawyer, W. H.; Paterson, A. R. P.

1982-01-01

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells...

An Approach for Leukemia Classification Based on Cooperative Game Theory

OpenAIRE

Torkaman, Atefeh; Charkari, Nasrollah Moghaddam; Aghaeipour, Mahnaz

2011-01-01

Hematological malignancies are the types of cancer that affect blood, bone marrow and lymph nodes. As these tissues are naturally connected through the immune system, a disease affecting one of them will often affect the others as well. The hematological malignancies include; Leukemia, Lymphoma, Multiple myeloma. Among them, leukemia is a serious malignancy that starts in blood tissues especially the bone marrow, where the blood is made. Researches show, leukemia is one of the common cancers ...

Leukemia among atomic bomb survivors during the 1980s

International Nuclear Information System (INIS)

Kusumi, Shizuyo; Matsuo, Tatsuki

1990-01-01

On the basis of the dosimetry system 1986, exposure doses were determined in a cohort of 86,502 subjects for the Life Span Study during the period 1950-1985. A total of 248 people were found to develop leukemia in Hiroshima and Nagasaki cities. This is an analysis of the 248 patients with leukemia in connection with exposure doses, years after A-bombing, age at the time of A-bombing, relative risk, and background. An average exposure dose was 0.20 Gy for Hiroshima and 0.22 Gy for Nagasaki. Relative risk for leukemia tended to show a linear increase in proportion to exposure doses. This was significant for acute myelocytic leukemia (AML), regardless of whether A-bomb survivors came from Hiroshima or Nagasaki. The younger the age at the time of A-bombing was, the higher excess relative risk for acute lymphocytic leukemia (ALL) and chronic myelocytic leukemia (CML) was. For AML, however, it was independent of the age at that time. These findings were similar in Hiroshima and Nagasaki A-bomb survivors, irrespective of age. As for non-exposed group, the incidence of CML was three times higher in Hiroshima citizen than Nagasaki citizen. Similarly, Hiroshima citizen had a 1.6 fold incidence of AML. There was no significant difference in the incidence of ALL between the cities. The incidences of both AML and ALL tended to increase more and more with aging, but the prevalences tended to increase in younger generation. An increased incidence of CML was associated with aging alone. (N.K.)

[Ultrastructure and Raman Spectral Characteristics of Two Kinds of Acute Myeloid Leukemia Cells].

Science.gov (United States)

Liang, Hao-Yue; Cheng, Xue-Lian; Dong, Shu-Xu; Zhao, Shi-Xuan; Wang, Ying; Ru, Yong-Xin

2018-02-01

To investigate the Raman spectral characteristics of leukemia cells from 4 patients with acute promyelocytic leukemia (M 3 ) and 3 patients with acute monoblastic leukemia (M 5 ), establish a novel Raman label-free method to distinguish 2 kinds of acute myeloid leukemia cells so as to provide basis for clinical research. Leukemia cells were collected from bone marrow of above-mentioned patients. Raman spectra were acquired by Horiba Xplora Raman spectrometer and Raman spectra of 30-50 cells from each patient were recorded. The diagnostic model was established according to principle component analysis (PCA), discriminant function analysis (DFA) and cluster analysis, and the spectra of leukemia cells from 7 patients were analyzed and classified. Characteristics of Raman spectra were analyzed combining with ultrastructure of leukemia cells. There were significant differences between Raman spectra of 2 kinds of leukemia cells. Compared with acute monoblastic leukemia cells, the spectra of acute promyelocytic leukemia cells showed stronger peaks in 622, 643, 757, 852, 1003, 1033, 1117, 1157, 1173, 1208, 1340, 1551, 1581 cm -1 . The diagnostic models established by PCA-DFA and cluster analysis could successfully classify these Raman spectra of different samples with a high accuracy of 100% (233/233). The model was evaluated by "Leave-one-out" cross-validation and reached a high accuracy of 97% (226/233). The level of macromolecules of M 3 cells is higher than that of M 5 . The diagnostic models established by PCA-DFA can classify these Raman spectra of different cells with a high accuracy. Raman spectra shows consistent result with ultrastructure by TEM.

The contribution of benzene to smoking-induced leukemia.

Science.gov (United States)

Korte, J E; Hertz-Picciotto, I; Schulz, M R; Ball, L M; Duell, E J

2000-04-01

Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts to estimate the leukemogenic potency of benzene. Using multiple-decrement life tables, we calculated lifetime risks of total leukemia and AML deaths for never, light, and heavy smokers. We repeated these calculations, removing the effect of benzene in cigarettes based on the estimated potencies. From these life tables we determined smoking-attributable risks and benzene-attributable risks. The ratio of the latter to the former constitutes the proportion of smoking-induced cases attributable to benzene. Based on linear potency models, the benzene in cigarette smoke contributed from 8 to 48% of smoking-induced total leukemia deaths [95% upper confidence limit (UCL), 20-66%], and from 12 to 58% of smoking-induced AML deaths (95% UCL, 19-121%). The inclusion of a quadratic term yielded results that were comparable; however, potency models with only quadratic terms resulted in much lower attributable fractions--all models substantially overestimate low-dose risk, linear extrapolations from empirical data over a dose range of 10- to 100-fold resulted in plausible predictions.

Immunogenicity moderation effect of interleukin-24 on myelogenous leukemia cells.

Science.gov (United States)

Yu, Xin; Miao, Jingcheng; Xia, Wei; Gu, Zong-Jiang

2018-04-01

Previous studies have shown that interleukin-24 (IL-24) has tumor-suppressing activity by multiple pathways. However, the immunogenicity moderation effect of IL-24 on malignant cells has not been explored extensively. In this study, we investigated the role of IL-24 in immunogenicity modulation of the myelogenous leukemia cells. Data show that myelogenous leukemia cells express low levels of immunogenicity molecules. Treatment with IL-24 could enhance leukemia cell immunogenicity, predominantly regulate leukemia cells to produce immune-associated cytokines, and improve the cytotoxic sensitivity of these cells to immune effector cells. IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. Moreover, IL-24 had marked effects on downregulating the expression of angiogenesis-related proteins vascular endothelial growth factor, cluster of differentiation (CD) 31, CD34, collagen IV and metastasis-related factors CD147, membrane type-1 matrix metalloproteinase (MMP), and MMP-2 and MMP-9 in transplanted tumors. These findings indicated novel functions of this antitumor gene and characterized IL-24 as a promising agent for further clinical trial for hematologic malignancy immunotherapy.

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Patient Version

Science.gov (United States)

Adult acute lymphoblastic leukemia (ALL; also called acute lymphocytic leukemia) is a blood cancer that often gets worse quickly if it is not treated. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about ALL in this expert-reviewed summary.

A case of acute lymphoblastic leukemia with abnormal brain CT scan after cranial irradiation for central nervous system leukemia

International Nuclear Information System (INIS)

Sato, Junko; Abe, Takanori; Watanabe, Tsutomu

1988-01-01

A 21-year-old woman with acute lymphoblastic leukemia presented with central neurologic symptoms immediately after the second irradiation (20 Gy to the brain and 10 Gy to the spinal cord) for central nervous system (CNS)-leukemia 3 years and 2 months after the first cranial irradiation with 20 Gy. White matter was depicted as diffusely high density area on CT; histology revealed necrosis of leukemic cells. In the present patient with repeated recurrent CNS-leukemia, leukemic cells seemed to have been damaged simultaneously after irradiation because of parenchymal widespread involvement of leukemic cells, resulting in brain edema, an increased intracranial pressure and parenchymal disturbance. This finding may have an important implication for the risk of cranial irradiation in the case of widespread involvement of leukemic cells. Re-evaluation of cranial irradiation in such cases is suggested. (Namekawa, K.)

Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

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Michele Cea

Full Text Available Aberrant histone deacetylase (HDAC activity is frequent in human leukemias. However, while classical, NAD(+-independent HDACs are an established therapeutic target, the relevance of NAD(+-dependent HDACs (sirtuins in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527 and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance.

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Kantarjian, Hagop; le Coutre, Phillipp; Cortes, Jorge; Pinilla-Ibarz, Javier; Nagler, Arnon; Hochhaus, Andreas; Kimura, Shinya; Ottmann, Oliver

2010-06-01

: INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. : A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. : INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and

Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

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Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

2017-03-01

Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

Supportive care for children with acute leukemia - Report of a survey on supportive care by the Dutch Childhood Leukemia Study Group. Part I

NARCIS (Netherlands)

Postma, A; Van Leeuwen, EF; Gerritsen, EJA; Roord, JJ; De vries-Hospers, HG

1998-01-01

The Dutch Childhood Leukemia Study Group celebrated its 20th anniversary by conducting a nationwide survey on supportive care for children with leukemia. Pediatricians were asked about daily practice and current perceptions with regard to supportive care. The results are discussed and compared to

An Approach for Leukemia Classification Based on Cooperative Game Theory

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Atefeh Torkaman

2011-01-01

Full Text Available Hematological malignancies are the types of cancer that affect blood, bone marrow and lymph nodes. As these tissues are naturally connected through the immune system, a disease affecting one of them will often affect the others as well. The hematological malignancies include; Leukemia, Lymphoma, Multiple myeloma. Among them, leukemia is a serious malignancy that starts in blood tissues especially the bone marrow, where the blood is made. Researches show, leukemia is one of the common cancers in the world. So, the emphasis on diagnostic techniques and best treatments would be able to provide better prognosis and survival for patients. In this paper, an automatic diagnosis recommender system for classifying leukemia based on cooperative game is presented. Through out this research, we analyze the flow cytometry data toward the classification of leukemia into eight classes. We work on real data set from different types of leukemia that have been collected at Iran Blood Transfusion Organization (IBTO. Generally, the data set contains 400 samples taken from human leukemic bone marrow. This study deals with cooperative game used for classification according to different weights assigned to the markers. The proposed method is versatile as there are no constraints to what the input or output represent. This means that it can be used to classify a population according to their contributions. In other words, it applies equally to other groups of data. The experimental results show the accuracy rate of 93.12%, for classification and compared to decision tree (C4.5 with (90.16% in accuracy. The result demonstrates that cooperative game is very promising to be used directly for classification of leukemia as a part of Active Medical decision support system for interpretation of flow cytometry readout. This system could assist clinical hematologists to properly recognize different kinds of leukemia by preparing suggestions and this could improve the treatment

Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0380 TITLE: Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias 5b. GRANT NUMBER...leukemias still have poor prognosis, particularly in the elderly, and require hematopoietic cell transplants to fully kill the tumor, which is both

Osteogenesis imperfecta and acute lymphoid leukemia: case report

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Gabriel David Tarud

2017-08-01

Discussion: It is well described that genetic and chromosomal abnormalities increase the risk of leukemia, however the relationship between osteogenesis imperfecta and acute lymphoblastic leukemia is rare. In the world literature, there are few cases mentioning this association. It is important to continue observing the occurrence of later cases, which allow describing if there is a direct relationship between these two entities.

Analysis of childhood leukemia mortality trends in Brazil, from 1980 to 2010

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Franciane F. Silva

2014-12-01

Full Text Available OBJECTIVE: Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010. METHODS: This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%. RESULTS: Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually, while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females. CONCLUSIONS: The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis.

Analysis of childhood leukemia mortality trends in Brazil, from 1980 to 2010.

Science.gov (United States)

Silva, Franciane F; Zandonade, Eliana; Zouain-Figueiredo, Glaucia P

2014-01-01

Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010. This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%. Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually), while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females) and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females). The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Improvement of Leukemia diagnose with molecular techniques

International Nuclear Information System (INIS)

Campos Rudin, M.E.

1997-01-01

The objective of this study was to contribute with new techniques to the clinical diagnosis and to the monitoring of mycloid chronic leukemias in Costa Rica. The same one achieved to determine that is viable to apply radioactive and non reactive methodologies, for the molecular detection of the Philadelphia chromosome.It also found that the application of techniques of cellular biology, helps to classify better the mycloide leukemias and the chronic mycloproliferatives and miclodisplaced disorders. (S. Grainger) [es

[Report of a case of megakaryoblastic leukemia].

Science.gov (United States)

Monteiro, J A; Timóteo, T; Elisário, L

1990-01-01

We diagnosed a 20 year old young girl, with clinical and laboratorial evidence of pancytopenia, an acute megakaryoblastic leukemia. The difficulty in arriving at this conclusion was only surpassed with the help of monoclonal antibodies. With the presentation of this case we approach the problematics in obtaining the diagnostic of the megakaryoblastic leukemia. This is fundamental, owing to the possibilities of morphological presentation under undifferentiated blasts or of the type M1 or L2 (FAB).

Drugs Approved for Leukemia

Science.gov (United States)

This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Mouse models in leukemia

NARCIS (Netherlands)

Voncken, J.W.

1995-01-01

Human Philadelphia-positive leukemia results from a balanced chromosomal translocation, which fuses the BCR gene on chromosome 22 to the ABL proto-oncogene on chromosome 9. The understanding of Ph-positive leukemogenesis has advanced enormously over

Viral Haemorrhagic Septicaemia Virus

DEFF Research Database (Denmark)

Olesen, Niels Jørgen; Skall, Helle Frank

2013-01-01

This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

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Sachiko Ezoe

2012-07-01

Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

Assembly of viral genomes from metagenomes

NARCIS (Netherlands)

S.L. Smits (Saskia); R. Bodewes (Rogier); A. Ruiz-Gonzalez (Aritz); V. Baumgärtner (Volkmar); M.P.G. Koopmans D.V.M. (Marion); A.D.M.E. Osterhaus (Albert); A. Schürch (Anita)

2014-01-01

textabstractViral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow

Viral commercials: the consumer as marketeer

NARCIS (Netherlands)

Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

2010-01-01

Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

Viral Infection in Renal Transplant Recipients

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Jovana Cukuranovic

2012-01-01

Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

Data quality in the Danish National Acute Leukemia Registry

DEFF Research Database (Denmark)

Ostgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Severinsen, Marianne Tang

2013-01-01

The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data.......The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data....

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

Science.gov (United States)

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

Leukemia and other cancers after radiotherapy and chemotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Boivin, J.F.; Hutchison, G.B.

1981-01-01

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was begun in 1976. This report describes 1,553 patients diagnosed with HD in 1940-75 and presents an analysis of follow-up findings through 1976. Twenty-seven cancers (excluding basal cell and squamous cell carcinomas of skin, trichoepitheliomas, and in situ carcinomas of cervix uteri) were observed 1 year or more after diagnosis of HD, including 6 leukemias. The relative risk (RR) of leukemia in patients treated with intensive chemotherapy with or without radiotherapy relative to general population incidence rates was 140 (95% confidence limits: 50,300). In the subgroup treated with both intensive radiotherapy and intensive chemotherapy, the RR of leukemia was 270 (95% confidence limits: 56,800). No leukemia occurred after treatment with intensive radiotherapy without chemotherapy. For cancers other than leukemia and for non-HD lymphomas, RR was generally not significantly different from the null value one

Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

Science.gov (United States)

Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

1989-04-01

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

Leukemia -- Chronic T-Cell Lymphocytic

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... social workers, and patient advocates. Cancer.Net Guide Leukemia - Chronic T-Cell Lymphocytic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic)

Science.gov (United States)

Ishii, Kazusa; Barrett, Austin J.

2016-01-01

There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID:26834952

Viral Metagenomics: MetaView Software

Energy Technology Data Exchange (ETDEWEB)

Zhou, C; Smith, J

2007-10-22

The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

Acute Pancreatitis in acute viral hepatitis

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S K.C.

2011-03-01

Full Text Available Introduction: The association of acute viral hepatitis and acute pancreatitis is well described. This study was conducted to find out the frequency of pancreatic involvement in acute viral hepatitis in the Nepalese population. Methods: Consecutive patients of acute viral hepatitis presenting with severe abdominal pain between January 2005 and April 2010 were studied. Patients with history of significant alcohol consumption and gall stones were excluded. Acute viral hepatitis was diagnosed by clinical examination, liver function test, ultrasound examination and confirmed by viral serology. Pancreatitis was diagnosed by clinical presentation, biochemistry, ultrasound examination and CT scan. Results: Severe abdominal pain was present in 38 of 382 serologically-confirmed acute viral hepatitis patients. Twenty five patients were diagnosed to have acute pancreatitis. The pancreatitis was mild in 14 and severe in 11 patients. The etiology of pancreatitis was hepatitis E virus in 18 and hepatitis A virus in 7 patients. Two patients died of complications secondary to shock. The remaining patients recovered from both pancreatitis and hepatitis on conservative treatment. Conclusions: Acute pancreatitis occurred in 6.5 % of patients with acute viral hepatitis. Cholelithiasis and gastric ulcers are the other causes of severe abdominal pain. The majority of the patients recover with conservative management. Keywords: acute viral hepatitis, acute pancreatitis, pain abdomen, hepatitis E, hepatitis A, endemic zone

Reclassification of leukemia among A-bomb survivors by French-American-British (FAB) classification, 1

International Nuclear Information System (INIS)

Matsuo, Tatsuki; Tomonaga, Masao; Bennett, J.M.

1987-09-01

The concordance rate for the French-American-British (FAB) reclassification diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined by a group of RERF hematologists and one of the members of the FAB cooperative gruop. The peripheral blood and/or bone marrow smears from 193 persons with leukemia or related disorder were reviewed. There was 85% agreement in the identification of leukemia types and subtypes. There was almost complete agreement for the diagnosis of non-FAB disorders (chronic myeloid leukemia and others) resulting in overall concordance of 88.2%. The conclusion from this remarkably high rate of concordance is that it is feasible to accurately apply the FAB classification system to the cases of A-bomb-related leukemia. These preliminary observations suggest that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders should be changed. (author)

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Science.gov (United States)

2015-06-03

Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Discrimination and classification of acute lymphoblastic leukemia cells by Raman spectroscopy

Science.gov (United States)

Managò, Stefano; Valente, Carmen; Mirabelli, Peppino; De Luca, Anna Chiara

2015-05-01

Currently, a combination of technologies is typically required to identify and classify leukemia cells. These methods often lack the specificity and sensitivity necessary for early and accurate diagnosis. Here, we demonstrate the use of Raman spectroscopy to identify normal B cells, collected from healthy patients, and three ALL cell lines (RS4;11, REH and MN60 at different differentiation level, respectively). Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for leukemia cell identification. Principal Component Analysis was finally used to confirm the significance of these markers for identify leukemia cells and classifying the data. The obtained results indicate a sorting accuracy of 96% between the three leukemia cell lines.

Childhood Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

2015-01-01

PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article...

Viral O-GalNAc peptide epitopes

DEFF Research Database (Denmark)

Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

2016-01-01

Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted o...

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

International Nuclear Information System (INIS)

Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion

2005-01-01

Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RARα and PLZF-RARα fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RARα from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells

Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study.

Science.gov (United States)

Metayer, Catherine; Milne, Elizabeth; Dockerty, John D; Clavel, Jacqueline; Pombo-de-Oliveira, Maria S; Wesseling, Catharina; Spector, Logan G; Schüz, Joachim; Petridou, Eleni; Ezzat, Sameera; Armstrong, Bruce K; Rudant, Jérémie; Koifman, Sergio; Kaatsch, Peter; Moschovi, Maria; Rashed, Wafaa M; Selvin, Steve; McCauley, Kathryn; Hung, Rayjean J; Kang, Alice Y; Infante-Rivard, Claire

2014-11-01

Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center. Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

Analysis of low Z elements in serum of patients with leukemias by SRTXRF

Energy Technology Data Exchange (ETDEWEB)

Canellas, Catarine G.L.; Jesus, Edgar F.O. de; Anjos, Marcelino J.; Lopes, Ricardo T., E-mail: marcelin@lin.ufrj.b, E-mail: catarine@lin.ufrj.b, E-mail: edgar@lin.ufrj.b, E-mail: marcelin@lin.ufrj.b, E-mail: ricardo@lin.ufrj.b [Federal University of Rio de Janeiro (UFRJ/COPPE), Rio de Janeiro, RJ (Brazil). Nuclear Engineering Program. Nuclear Instrumentation Lab.; Carvalho, Silvia M.F., E-mail: silvia@hemorio.rj.gov.b [State Institute of Hematology Arthur de Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ (Brazil)

2009-07-01

Leukemia is a disease that occurs all over the world. Leukemia is a type of cancer. All cancers begin in cells, which make up blood and other tissues. Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. Leukemia is a kind of cancer that begins in blood cells. There are four common types of leukemia: Chronic Myelogenous Leukemia (CML), Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Leukemia (CLL) and Acute Lymphocytic Leukemia (ALL). In this work, low Z elements were determined in serum of patients with four groups of leukemia (CML, AML, CLL and ALL) and control group (CG) or healthy subjects using Total Reflection X-Ray Fluorescence induced by Synchrotron Radiation (SRTXRF). We studied thirty patients - male gender and feminine gender - with ages ranging from 18 to 60 years, suffering from CML, AML, CLL, ALL and thirty healthy volunteers aged 18 to 60 years. All the serum samples were collected from people who live in the urban area of Rio de Janeiro City/Brazil. All of them were submitted to medical history. This study was performed with the approval of the ethics committee. It was possible to determine the elemental concentrations of the following six elements: Na, P, S, Cl, K and Ca. By using t-test it could be seen significant differences (alpha = 0.05) between groups of healthy subjects and four groups of leukemia. The t- test showed real differences among the elemental concentrations. Thus, our findings indicate that the elements can be directly related to the biochemical processes in leukemias. The significant differences found between the groups may be indicators of these diseases. This could help biomedical field with regard to early diagnosis and improved medical treatment. (author)

Analysis of low Z elements in serum of patients with leukemias by SRTXRF

International Nuclear Information System (INIS)

Canellas, Catarine G.L.; Jesus, Edgar F.O. de; Anjos, Marcelino J.; Lopes, Ricardo T.

2009-01-01

Leukemia is a disease that occurs all over the world. Leukemia is a type of cancer. All cancers begin in cells, which make up blood and other tissues. Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. Leukemia is a kind of cancer that begins in blood cells. There are four common types of leukemia: Chronic Myelogenous Leukemia (CML), Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Leukemia (CLL) and Acute Lymphocytic Leukemia (ALL). In this work, low Z elements were determined in serum of patients with four groups of leukemia (CML, AML, CLL and ALL) and control group (CG) or healthy subjects using Total Reflection X-Ray Fluorescence induced by Synchrotron Radiation (SRTXRF). We studied thirty patients - male gender and feminine gender - with ages ranging from 18 to 60 years, suffering from CML, AML, CLL, ALL and thirty healthy volunteers aged 18 to 60 years. All the serum samples were collected from people who live in the urban area of Rio de Janeiro City/Brazil. All of them were submitted to medical history. This study was performed with the approval of the ethics committee. It was possible to determine the elemental concentrations of the following six elements: Na, P, S, Cl, K and Ca. By using t-test it could be seen significant differences (α = 0.05) between groups of healthy subjects and four groups of leukemia. The t- test showed real differences among the elemental concentrations. Thus, our findings indicate that the elements can be directly related to the biochemical processes in leukemias. The significant differences found between the groups may be indicators of these diseases. This could help biomedical field with regard to early diagnosis and improved medical treatment. (author)

Adaptive immunity to leukemia is inhibited by cross-reactive induced regulatory T cells

OpenAIRE

Manlove, Luke S.; Berquam-Vrieze, Katherine E.; Pauken, Kristen E.; Williams, Richard T.; Jenkins, Marc K.; Farrar, Michael A.

2015-01-01

BCR-ABL+ acute lymphoblastic leukemia patients have transient responses to current therapies. However, the fusion of BCR to ABL generates a potential leukemia-specific antigen that could be a target for immunotherapy. We demonstrate that the immune system can limit BCR-ABL+ leukemia progression although ultimately this immune response fails. To address how BCR-ABL+ leukemia escapes immune surveillance, we developed a peptide: MHC-II tetramer that labels endogenous BCR-ABL-specific CD4+ T cell...

TBI parameters and relapse of acute leukemia

International Nuclear Information System (INIS)

Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

1994-01-01

The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

Science.gov (United States)

Kimura, Shun-Ichi; Fujita, Hiroyuki; Kato, Hideaki; Hiramoto, Nobuhiro; Hosono, Naoko; Takahashi, Tsutomu; Shigeno, Kazuyuki; Hatsumi, Naoko; Minamiguchi, Hitoshi; Miyatake, Junichi; Handa, Hiroshi; Akiyama, Nobu; Kanda, Yoshinobu; Yoshida, Minoru; Kiyoi, Hitoshi; Miyazaki, Yasushi; Naoe, Tomoki

2017-11-01

We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.

Science.gov (United States)

Scott, A A; Head, D R; Kopecky, K J; Appelbaum, F R; Theil, K S; Grever, M R; Chen, I M; Whittaker, M H; Griffith, B B; Licht, J D

1994-07-01

We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and

Review of diagnosis and classification of leukemias that occurred in A-bomb survivors (preliminary report)

Energy Technology Data Exchange (ETDEWEB)

Matsuo, T; Tomonaga, M; Ichimaru, M; Kamata, N; Kuramoto, A

1984-11-01

According to the current knowledge of diagnosis and classification, a review of 157 patients who had developed leukemia before June 30, 1967 was made. The incidence of acute leukemia decreased slightly among A-bomb survivors in Hiroshima; however, the incidence of acute lymphatic leukemia (ALL) increased. The number of chronic myeloid leukemia (CML) was unchanged. The frequency of CML implied that A-bombing damaged stem cells. Among A-bomb survivors in Nagasaki, although the number of acute non-lymphatic leukemia decreased, the number of ALL was unchanged. Adult T-cell leukemia (ATL) was diagnosed in 7 A-bomb survivors, confirming that Nagasaki is an endemic area for ATL. These preliminary results seem to be of importance in elucidating the mechanism of leukemia developing among A-bomb survivors. (Namekawa, K.).

Review of diagnosis and classification of leukemias that occurred in A-bomb survivors (preliminary report)

International Nuclear Information System (INIS)

Matsuo, Tatsuki; Tomonaga, Masao; Ichimaru, Michito; Kamata, Nanao; Kuramoto, Atsushi.

1984-01-01

According to the current knowledge of diagnosis and classification, a review of 157 patients who had developed leukemia before June 30, 1967 was made. The total number of acute leukemia slightly decreased among A-bomb survivors in Hiroshima; however, the number of acute lymphatic leukemia (ALL) increased. The number of chronic myeloid leukemia (CML) was unchanged. The frequency of CML implied that A-bombing damaged stem cells in a high incidence. Among A-bomb survivors in Nagasaki, although the number of acute non-lymphatic leukemia decreased, the number of ALL was unchanged. Adult T-cell leukemia (ATL) was diagnosed in 7 A-bomb survivors, confirming that Nagasaki is an endemic area for ATL. These preliminary results seem to be of importance in elucidating the mechanism of leukemia developiong among A-bomb survivors. (Namekawa, K.)

Viral infections in transplant recipients.

Science.gov (United States)

Razonable, R R; Eid, A J

2009-12-01

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

[Viral hepatitis in travellers].

Science.gov (United States)

Abreu, Cândida

2007-01-01

Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

Brick mortar exposure and chronic lymphocytic leukemia.

Science.gov (United States)

Markovic-Denic, L; Jankovic, S; Marinkovic, J; Radovanovic, Z

1995-01-01

A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL.

Brick mortar exposure and chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Markovic-Denic, Lj.; Jankovic, S.; Marinkovic, J.; Radovanovic, Z.

1995-01-01

A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author)

Case report 429: Adult T-cell leukemia (ATL)

International Nuclear Information System (INIS)

Aoki, Jun; Yamamoto, Itsuo; Hino, Megumu; Torizuka, Kanji; Kyoto Univ.; Uchiyama, Takahashi; Uchino, Haruto

1987-01-01

The radiological and pathological skeletal manifestations in a case of adult T-cell leukemia are presented. The authors have emphasized the presence of multiple areas of localized subperiosteal resorption as a helpful finding in the differential diagnosis between adult T-cell leukemia and multiple myeloma and hyperparathyroidism. A possible mechanism for these radiological features and its similarity to those of other T-cell malignancies are discussed briefly. (orig./SHA)

Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

Science.gov (United States)

Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

2017-04-01

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

DEFF Research Database (Denmark)

Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

2011-01-01

.2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...

Assembly of viral genomes from metagenomes

Directory of Open Access Journals (Sweden)

Saskia L Smits

2014-12-01

Full Text Available Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

Science.gov (United States)

2018-05-14

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Viral marketing as epidemiological model

OpenAIRE

Rodrigues, Helena Sofia; Fonseca, Manuel

2015-01-01

In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of...

Ethical Considerations in Research Participation Virality.

Science.gov (United States)

Ellis-Barton, Carol

2016-07-01

This article seeks to commence and encourage discussion around the upcoming ethical challenges of virality in network structures. When the call for participation in a research project on lupus in Ireland went from an advertisement in a newsletter to a meme (unit of transmissible information) on a closed Facebook page, the ethical considerations of virality were raised. The article analyzes the Association of Internet Researchers guidelines, Facebook policies, and the context of privacy in relation to virality. Virality creates the leverage for methodological pluralism. The nature of the inquiry can determine the method rather than the other way around. Viral ethical considerations are evolving due to the cyber world becoming the primary meme of communication, with flexibility in the researcher's protocol providing opportunities for efficient, cost-effective, and diverse recruitment. © The Author(s) 2016.

The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

Directory of Open Access Journals (Sweden)

Jie Zhang

Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.

Directory of Open Access Journals (Sweden)

Maikel L Colli

2011-09-01

Full Text Available The rise in type 1 diabetes (T1D incidence in recent decades is probably related to modifications in environmental factors. Viruses are among the putative environmental triggers of T1D. The mechanisms regulating beta cell responses to viruses, however, remain to be defined. We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA and a diabetogenic enterovirus (Coxsackievirus B5. Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR promotes eIF2α phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1. Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis. Indeed, Bim knockdown prevented both dsRNA- and Coxsackievirus B5-induced beta cell death, and counteracted the proapoptotic effects of Mcl-1 silencing. These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections.

Incidence and mortality trends of leukemia and lymphoma in Croatia, 1988-2009

Science.gov (United States)

Novak, Ina; Jakšić, Ozren; Kuliš, Tomislav; Batinjan, Katarina; Znaor, Ariana

2012-01-01

Aim To investigate the time trends of leukemia and lymphoma in Croatia from 1988-2009, compare them with trends in other populations, and identify possible changes. Methods The data sources were the Croatian National Cancer Registry for incidence data, Croatian Bureau of Statistics for the numbers of deaths, and United Nations population estimates. Joinpoint regression analysis using the age-standardized rates was used to analyze incidence and mortality trends. Results Acute lymphoblastic leukemia and chronic lymphocytic leukemia incidence did not significantly change. Acute myeloid leukemia incidence significantly increased in women, with estimated annual percentage change (EAPC) of 2.6% during the whole period, and in men since 1998, with EAPC of 3.2%. Chronic myeloid leukemia incidence significantly decreased in women (EAPC -3.7%) and remained stable in men. Mortality rates were stable for both lymphoid and myeloid leukemia in both sexes. Hodgkin lymphoma non-significantly increased in incidence and significantly decreased in mortality (EAPCs of -5.6% in men and -3.7% in women). Non-Hodgkin lymphoma significantly increased in incidence in women (EAPC 3.2%) and non-significantly in men and in mortality in both men (EAPC 1.6%) and women (EAPC 1.8%). Conclusion While Croatia had similar leukemia and lymphoma incidence trends as the other countries, the mortality trends were less favorable than in Western Europe. The lack of declines of leukemia incidence and non-Hodgkin lymphoma mortality could be attributed to late introduction of optimal therapies. As currently the most up-to-date diagnostics and treatments are available and covered by health insurance, we expect more favorable trends in the future. PMID:22522989

The MLL recombinome of acute leukemias in 2017.

Science.gov (United States)

Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; Zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

2018-02-01

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

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Carolin Vegvari

Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

Prevalence of periodontal disease in children with leukemia disease and thalassemia

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Hardianti Maulidita

2016-06-01

Full Text Available Various periodontal disease can occur in children and adolescents. Some can take place quickly and periodontal tissue damage. Several previous studies indicate that systemic diseases associated with periodontal disease in children. This study aims to determine the prevalence of periodontal disease in children with leukemia and thalassemia. The design study is a cross-sectional approach. Periodontal pocket depth measurements performed using the WHO standard of measurement. The samples in this study were drawn from the entire population using accidental sampling method. Sampled population was pediatric patients with leukemia and thalassemia. These patients were undergoing treatment in hospital Wahidin Sudirohusodo Hospital Makassar. During the study, children with leukemia as many as 18 patients and children with thalassemia by 8 patients. Distribution of pediatric patients suffering from leukemia by CPITN score; score of 2 as many as 10 patients (55.6%, a score of 1 as 6 patients (33.3%, and  score of 0 as many as 2 patients (11.1%. CPITN score in children with thalassemia; scores 2 in 1 patient (12.5%, a score of 1 as 6 patients (75%, and score of 0 by 1 patient (12.5%. Children who have leukemia and thalassemia, showed the rate of occurrence of different periodontal disease. Children with leukemia shows the level of periodontal disease is higher than in children with thalassemia disease.

Stages of Chronic Lymphocytic Leukemia

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... of the lymph system . Having relatives who are Russian Jews or Eastern European Jews. Signs and symptoms ... information about clinical trials is also available. To Learn More About Chronic Lymphocytic Leukemia For more information ...

Differential effects of atomic bomb irradiation in inducing major leukemia types

International Nuclear Information System (INIS)

Tomonaga, Masao; Matsuo, Tatsuki; Carter, R.L.

1993-05-01

In this report we utilize data from the additional 517 cases from the leukemia registry together with the Life Span Study (LSS) cohort data to study the effects of atomic bomb irradiation on major leukemia types. The French-American-British classification and other improved diagnostic methods were used to reclassify cases into 21 categories, including new disease entities such as adult T-cell leukemia (ATL). These categories were then grouped into four major types for analysis: (1) acute lymphocytic leukemia (ALL), (2) acute myeloid leukemia (AML) including myelodysplastic syndromes (MDS), (3) chronic myeloid leukemia (CML), and (4) OTHER types including ATL. Analyses of radiation effects were based on the updated Dosimetry System 1986(DS86). Incidence rates of all four leukemia types increased with increasing exposure level. The effects of radiation were significantly greater on the incidence of ALL and CML than on that of AML and OTHER. In the two lowest dose categories (1-49 and 50-499 mGy), estimated incidence either remained constant or increased slightly as the population of survivors aged. In the two highest dose categories (500-1,499 and ≥ 1,500 mGy). Among unexposed persons, the estimated risk of CML in Nagasaki relative to Hiroshima was significantly less than that of AML, whereas that of OTHER types was significantly greater. The time to onset of ALL, AML, and CML declined with increasing dose. The rate of decline, however, was greater for ALL and CML than for AML. The resulting differences at high doses reflect shorter incubation times for atomic-bomb-induced ALL and CML than for AML. (J.P.N.)

Overexpression of chitinase like protein YKL-40 in leukemia patients

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Anil K. Hurmale

2013-01-01

Full Text Available YKL-40 is a member of mammalian chitanase (CHI3L1, expressed and secreted by several types of solid tumor cells, inflammatory cells and stem cells. The precise physiological role of YKL-40 in cancer is still not clear and it is suggested that it play a role in cancer cell proliferation, differentiation, metastatic potential, cell attachment and migration, reorganization and tissue remodeling.The aim of the study was to check the appearance of YKL-40 in leukemic cells and over-expression of YKL-40 in the plasma of leukemia patients in comparison to healthy controls, and find whether YKL-40 could serve as a peripheral biomarker for leukemia. The study was conducted between July 2012 and March 2013 and included 67 volunteers, 55 having leukemia at the stage of diagnosis ofthe disease and 12 normal healthy volunteers. YKL-40 levels were determined in all plasma samples using the YKL-40 enzyme-linked immunosorbent assay (ELISA kit and expression of YKL-40 was observed by using immunocytochemical (ICC analysis. YKL-40 plasma levels differed significantly between patients with leukemia and the normal healthy volunteers (P=<0.001 and YKL-40 was positively expressed in all four types of leukemia (AML, ALL, CLL and CML specimens.

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

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Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-04-30

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

Brick mortar exposure and chronic lymphocytic leukemia

Energy Technology Data Exchange (ETDEWEB)

Markovic-Denic, Lj; Jankovic, S [Institute of Epidemiology, Faculty of Medicine, Belgrade (Yugoslavia); Marinkovic, J [Institute of Social Medicine, Statistics and Healt Research, Faculty of Medicine, Belgrade (Yugoslavia); Radovanovic, Z [Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, 13110 Safat (Kuwait)

1996-12-31

A case-control study of 130 patients with chronic lymphocytic leukemia (CLL) and 130 controls matched with respect to sex, age (2 years), type of residence, (urban-rural) and area of residence (according to the national per capita income) was carried out. Conditional logistic regression analysis showed that, apart of four risk factors already described in the literature (work in a hazardous industry, hair dye use, family history of leukemia and exposure to electromagnetic radiation), brick mortar exposure was also significantly related to CLL. (author) 1 tab., 30 refs.

Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

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Katja Pfafferott

2011-02-01

Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

Serum adiponectin levels are inversely correlated with leukemia: A meta-analysis

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Jun-Jie Ma

2016-01-01

Conclusion: Our meta-analysis suggested that serum ADPN levels may be inversely correlated with leukemia, and ADPN levels can be used as an effective biologic marker in early diagnosis and therapeutic monitoring of leukemia.

Treatment Options for Childhood Acute Myeloid Leukemia, Childhood Chronic Myelogenous Leukemia, Juvenile Myelomonocytic ...

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... can affect the blood and bone marrow. Transient abnormal myelopoiesis (TAM) TAM is a disorder of the bone marrow that can develop in ... is sometimes used to treat MDS or transient abnormal myelopoiesis (TAM). ... caused by the disease or its treatment. All patients with leukemia receive ...

Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

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2018-05-24

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

Modifying factors of radiation induced myeloid leukemia of C3H/He mouse

International Nuclear Information System (INIS)

Yoshida, Kazuko; Nishimura, Mayumi; Nemoto, Kumie; Seki, Masatoshi

1989-01-01

The first experiment examined modifying factors, such as adrenocortical hormones, inflammatory reaction, and surgical stress, for radiation induced myeloid leukemia in C3H/He mice. The incidence of myeloid leukemia was not affected by a solitary subcutaneous injection of one mg of prednisolone acetate (predonine), but increased significantly by whole body irradiation, immediately followed by predonine. Augumentated effects of predonine was found in the 0.47 Gy, 1.42 Gy, and 2.84 Gy irradiated groups, but not found in the 4.73 Gy irradiated group. These results suggest that predonine itself did not have any effect on initiation of leukemogenesis, but promoted the incidence of radiation-induced myeloid leukemia. In the next experiment determining whether the incidence of myeloid leukemia was increased with stimulation of hematopoietic tissues, mice were inserted a piece of cellulose acetate membrane (CAM) into the peritoneal cavity. In the non-irradiated group of mice, CAM insertion did not affect the incidence of myeloid leukemia at all. The incidence of leukemia increased significantly by CAM insertion combined with irradiation of 2.84 Gy. Mice suffered from both surgical stress and inflammatory reaction after CAM insertion. Therefore, surgical stress was considered responsible for the development of radiation-induced leukemia. (Namekawa, K)

Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

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Guldane Cengiz Seval

2015-03-01

Full Text Available The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML in adolescent and young adult patients (AYAs may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma.

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Kast, Richard E

2008-10-01

This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid (ATRA, also termed tretinoin) exerts an anti-viral effect against hepatitis C virus (HCV) in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-a activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-a responses in these cancers.

Bile acids for viral hepatitis

DEFF Research Database (Denmark)

Chen, Weikeng; Liu, J; Gluud, C

2007-01-01

Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.