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Sample records for acute leukemia jurkat

  1. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways.

    Yang, Tingfang; Yao, Shuluan; Zhang, Xianfeng; Guo, Yan

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro), the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 μg/mL Andro could significantly induce Jurkat cells' apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro's dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days. PMID:27114702

  2. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways

    Yang T

    2016-04-01

    Full Text Available Tingfang Yang,1 Shuluan Yao,2 Xianfeng Zhang,3 Yan Guo2 1Department of Pediatrics, Jining No 1 People’s Hospital, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Jining Medical University Affiliated Hospital, Shandong Province, People’s Republic of China; 3Department of Psychiatry, Jining Psychiatric Hospital, Shandong Province, People’s Republic of China Abstract: T-cell acute lymphoblastic leukemia (T-ALL as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro, the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 µg/mL Andro could significantly induce Jurkat cells’ apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro’s dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days. Keywords: andrographolide, PI3K, AKT, Burkitt lymphoma, Jurkat cell

  3. Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

    Hojka-Osinska, Anna, E-mail: hojka@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Ziolo, Ewa, E-mail: ziolo@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Rapak, Andrzej, E-mail: rapak@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer The combination of fenretinide and indomethacin induces a high level of cell death. Black-Right-Pointing-Pointer Apoptotic pathway is caspase-independent. Black-Right-Pointing-Pointer Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.

  4. Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

    Highlights: ► The combination of fenretinide and indomethacin induces a high level of cell death. ► Apoptotic pathway is caspase-independent. ► Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug–indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.

  5. Vitamin E synthetic derivate-TPGS-selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia.

    Ruiz-Moreno, Cristian; Jimenez-Del-Rio, Marlene; Sierra-Garcia, Ligia; Lopez-Osorio, Betty; Velez-Pardo, Carlos

    2016-09-01

    D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of natural vitamin E commonly used as a drug delivery agent. Recently, TPGS alone has been reported to induce cell death in lung, breast and prostate cancer. However, the effect of TPGS on cancer cell viability remains unclear. Thus, this study was aimed to evaluate the cytotoxic effect of TPGS on human periphral blood lymphocytes (PBL) and on T cell acute lymphocytic leukemia (ALL) Jurkat clone E6-1 cells and its possible mechanism of action. PBL and Jurkat cells were treated with TPGS (10, 20, 40, 60, and 80 μM), and morphological changes in the cell nucleus, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species levels were determined by immune-fluorescence microscopy and flow cytometry. Cellular apoptosis markers were also evaluated by immunocytochemistry. In this study, TPGS induced apoptotic cell death in Jurkat cells, but not in PBL, in a dose-response manner with increasing nuclear DNA fragmentation, increasing cell cycle arrest, and decreasing ΔΨm. Additionally, TPGS increased dichlorofluorescein fluorescence intensity, indicative of H2O2 production, in a dose-independent fashion. TPGS increased DJ-1 Cys(106)-sulfonate, as a marker of intracellular stress and induced the activation of NF-κB, p53 and c-Jun transcription factors. Additionally, it increased the expression of apoptotic markers Bcl-2 related pro-apoptotic proteins Bax and PUMAand activated caspase-3. The antioxidant N-acetyl-L-cysteine and known pharmacological inhibitors protected the cells from the TPGS induced effects. In conclusion, TPGS selectively induces apoptosis in Jurkat cells through two independent but complementary H2O2-mediated signaling pathways. Our findings support the use of TPGS as a potential treatment for ALL. PMID:27364951

  6. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  7. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways

    Yang T; Yao S; Zhang X; Guo Y

    2016-01-01

    Tingfang Yang,1 Shuluan Yao,2 Xianfeng Zhang,3 Yan Guo2 1Department of Pediatrics, Jining No 1 People’s Hospital, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Jining Medical University Affiliated Hospital, Shandong Province, People’s Republic of China; 3Department of Psychiatry, Jining Psychiatric Hospital, Shandong Province, People’s Republic of China Abstract: T-cell acute lymphoblastic leukemia (T-ALL) as a pr...

  8. Methylation of Gene CHFR Promoter in Acute Leukemia Cells

    GONG Hui; LIU Wengli; ZHOU Jianfeng; XU Huizhen

    2005-01-01

    Summary: In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt-4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myelocytic leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.

  9. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  10. Mixed phenotype acute leukemia

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  11. Pro-apoptotic effect of Persea americana var. Hass (avocado) on Jurkat lymphoblastic leukemia cells.

    Bonilla-Porras, Angelica R; Salazar-Ospina, Andrea; Jimenez-Del-Rio, Marlene; Pereañez-Jimenez, Andres; Velez-Pardo, Carlos

    2013-11-01

    Abstract Context: Therapy for leukemia has a limited efficacy. There is a need to search for alternative anti-leukemia therapies. Persea americana Mill var. Hass (Lauraceae) is a tropical fruit (avocado) that might be used against cancer. Objective: To investigate whether P. americana induces death in Jurkat lymphoblastic leukemia cells. Materials and methods: Four ethanol extracts (0.1, 0.5, 1, 2 and 5 mg/mL) from avocado fruit (endocarp, whole seed, seed and leaves) were analyzed against Jurkat cells. Hydrogen peroxide generation by oxidation of 2',7'-dichlorodihydrofluorescein diacetate to the fluorescent compound 2',7'-dichlorfluorescein assay, acridine orange/ethidium bromide staining, flow cytometry analysis of annexin-V/7-amino-actinomycin, mitochondrial membrane potential and immunocytochemistry detection of transcription factor p53, caspase-3 and apoptosis-inducing factor (AIF) were evaluated. Results: Endocarp, seed, whole seed, and leaf (0.1 mg/mL) extracts induced significant apoptosis in Jurkat cells (p americana extracts function as a pro-apoptotic compound. Leukemic cells are eliminated through an oxidative stress mechanism. This study contributes to the understanding of the molecular mechanism of the avocado and its therapeutic action on leukemia. PMID:24188375

  12. Diversity and Complexity of Ceramide Generation After Exposure of Jurkat Leukemia Cells to Irradiation

    Purpose: To define which intracellular pools of sphingomyelin and ceramide are involved in the triggering of apoptosis of Jurkat leukemia cells in response to γ-ray exposure. Methods and Materials: We examined the kinetics of ceramide generation at the whole-cell level and in different subcellular compartments (plasma membrane rafts, mitochondria, and endoplasmic reticulum) after irradiation with photons. Ceramide was measured by high-performance liquid chromatography or after pulse labeling experiments, and the presence of sphingomyelinase within mitochondria was assessed by electron microscopy. Results: Irradiation of Jurkat leukemia cells resulted in the sequential triggering of sphingomyelin hydrolysis, followed by de novo synthesis that led to a late ceramide response (from 24 h) correlated with the triggering of apoptosis. At the subcellular level, pulse-label experiments, using [3H]-palmitate as a precursor, strengthened the involvement of the radiation-induced sphingomyelin breakdown and revealed a very early peak (15 min) of ceramide in plasma membrane rafts. A second peak in mitochondria was measured 4 h after irradiation, resulting from an increase of the sphingomyelin content relating to the targeting of acid sphingomyelinase toward this organelle. Conclusion: These data confirm that ceramide is a major determinant in the triggering of radiation-induced apoptosis and highlight the complexity of the sequential compartment-specific ceramide-mediated response of Jurkat leukemia cells to γ-rays

  13. Congenital acute megakaryocytic leukemia

    N B Mathur

    2011-01-01

    Full Text Available Congenital leukemia (CL is an extremely rare disorder in the newborn, significant proportion of which is of myeloid origin, primarily of M4 or M5 morphology. As compared to pediatric leukemia, CL is a more aggressive disease. Acute myeloid leukemia (AML-M7 or acute megakaryocytic leukemia is a rare type of AML with an incidence of 0.5 per million per year. Median age of presentation is 6 years, and children may present with a broad variety of symptoms including low-grade fever, diarrhea, easy bruising, failure to gain weight and life-threatening conditions.

  14. The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells.

    Xinli Liu

    Full Text Available Deregulation of Nuclear Transcription Factor-κB (NF-κB and Jun N-terminal kinase (JNK signaling is commonly detected in leukemia, suggesting an important role for these two signaling pathways in the pathogenesis of leukemia. In this study, using Jurkat cells, an acute T-lymphoblastic leukemia (T-ALL cell line, we evaluated the effects of an NF-κB inhibitor and a JNK inhibitor individually and in combination on the proliferation, survival and clonogenic capacity of leukemic cells. We found that leukemic stem/progenitor cells (LSPCs were more sensitive to NF-κB inhibitor treatment than were healthy hematopoietic stem/progenitor cells (HSPCs, as shown by a reduction in the clonogenic capacity of the former. Inactivation of NF-κB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-κB inhibitor on LSPCs but prevented such repression in HSPCs. Our data suggest that JNK signaling stimulates proliferation/survival in LSPCs but is a death signal in HSPCs. The combination of NF-κB inhibitor and JNK inhibitor might provide a better treatment for T-ALL leukemia by synergistically killing LSPCs while simultaneously preventing the death of normal HPCs.

  15. The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells.

    Liu, Xinli; Zhang, Jun; Li, Jing; Volk, Andrew; Breslin, Peter; Zhang, Jiwang; Zhang, Zhou

    2014-01-01

    Deregulation of Nuclear Transcription Factor-κB (NF-κB) and Jun N-terminal kinase (JNK) signaling is commonly detected in leukemia, suggesting an important role for these two signaling pathways in the pathogenesis of leukemia. In this study, using Jurkat cells, an acute T-lymphoblastic leukemia (T-ALL) cell line, we evaluated the effects of an NF-κB inhibitor and a JNK inhibitor individually and in combination on the proliferation, survival and clonogenic capacity of leukemic cells. We found that leukemic stem/progenitor cells (LSPCs) were more sensitive to NF-κB inhibitor treatment than were healthy hematopoietic stem/progenitor cells (HSPCs), as shown by a reduction in the clonogenic capacity of the former. Inactivation of NF-κB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-κB inhibitor on LSPCs but prevented such repression in HSPCs. Our data suggest that JNK signaling stimulates proliferation/survival in LSPCs but is a death signal in HSPCs. The combination of NF-κB inhibitor and JNK inhibitor might provide a better treatment for T-ALL leukemia by synergistically killing LSPCs while simultaneously preventing the death of normal HPCs. PMID:25526629

  16. The Synergistic Repressive Effect of NF-κB and JNK Inhibitor on the Clonogenic Capacity of Jurkat Leukemia Cells

    Liu, Xinli; Zhang, Jun; Li, Jing; Volk, Andrew; Breslin, Peter; Zhang, Jiwang; Zhang, Zhou

    2014-01-01

    Deregulation of Nuclear Transcription Factor-κB (NF-κB) and Jun N-terminal kinase (JNK) signaling is commonly detected in leukemia, suggesting an important role for these two signaling pathways in the pathogenesis of leukemia. In this study, using Jurkat cells, an acute T-lymphoblastic leukemia (T-ALL) cell line, we evaluated the effects of an NF-κB inhibitor and a JNK inhibitor individually and in combination on the proliferation, survival and clonogenic capacity of leukemic cells. We found that leukemic stem/progenitor cells (LSPCs) were more sensitive to NF-κB inhibitor treatment than were healthy hematopoietic stem/progenitor cells (HSPCs), as shown by a reduction in the clonogenic capacity of the former. Inactivation of NF-κB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-κB inhibitor on LSPCs but prevented such repression in HSPCs. Our data suggest that JNK signaling stimulates proliferation/survival in LSPCs but is a death signal in HSPCs. The combination of NF-κB inhibitor and JNK inhibitor might provide a better treatment for T-ALL leukemia by synergistically killing LSPCs while simultaneously preventing the death of normal HPCs. PMID:25526629

  17. Acute lymphoblastic leukemia (ALL)

    Jeha S, Pui CH. Clinical manifestations and treatment of acute lymphoblastic leukemia in children. In: Hoffman R, Benz EJ Jr, Silberstein LE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. ...

  18. Apoptosis-inducing effects of jujube (Zǎo) seed extracts on human Jurkat leukemia T cells

    Taechakulwanijya, Natthanan; Weerapreeyakul, Natthida; Barusrux, Sahapat; Siriamornpun, Sirithorn

    2016-01-01

    Background Jujube (Zǎo) seeds exhibited anticancer effects and used in Chinese medicine for many years. This study aims to investigate the apoptosis-inducing effects of seed extracts from eight different cultivated species (‘Apple’, ‘Bombay’, ‘Jumbo’, ‘Kaew’, ‘Nomsod’, ‘Rianthong’, ‘Samros’, and ‘Taiwan’) on human Jurkat leukemia T cells. Methods We evaluated the effects of seed extracts from eight jujube cultivated species on human Jurkat leukemia T cells. The crude seed extracts were prepar...

  19. Childhood Acute Lymphoblastic Leukemia

    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 was...

  20. Acute myelogenous leukemia (AML) -- children

    ... Leung WH, Pounds S, Cao X, e t al. Definition of cure in childhood acute myeloid leukemia. Cancer . ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  1. Acute Lymphocytic Leukemia

    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 ...

  2. Acute Myeloid Leukemia

    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 ...

  3. Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition

    Yan-min ZHAO; Qian ZHOU; Yun XU; Xiao-yu LAI; He HUANG

    2008-01-01

    Aim:To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. Methods:Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progres-sion and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. Results:Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the pro-tein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion:Rapamycin displayed a potent antileukemic effect in the human T-cell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.

  4. Acute childhood leukemia: Nursing care

    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

  5. General Information about Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  6. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  7. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  8. General Information about Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  9. Stages of Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  10. Stages of Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  11. Treatment Options for Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  12. Treatment Options for Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  13. Acute lymphocytic Leukemia masquerading as acute osteomyelitis

    Two children each developed a focal destructive bone lesion accompanied by intermittent fever, swelling, tenderness and elevated ESR. Blood counts were normal; bone marrow aspiration showed acute leukemia. The bone lesions healed in both patients after anti-leukemic therapy. We suggest that the similar roentgenographic appearance of osteomyelitis, bone infarction and focal destructive lesions in leukemia probably reflects a common, basically ischemic process of bone. (orig.)

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

    2016-04-07

    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

  15. Polyradiculoneuritis revealing an acute monoblastic leukemia 5

    Wafa Allam; Hassan Errihani; Yahya Hsaini

    2010-01-01

    Acute polyradiculoneuritis has been frequently reported in association with malignant disorders, especially those of the lymphoid system. To date, there have been no reported cases of acute monoblastic leukemia associated with this polyradiculopathy. The authors tell us about a very rare case of leukemia presenting as acute monoblastic leukemia 5 (AML5) in a 28 years old patient from Morroco

  16. Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

    Bernt, Kathrin M.; Armstrong, Scott A.

    2009-01-01

    Leukemias and other cancers have been proposed to contain a subpopulation of cells that display characteristics of stem cells, and which maintain tumor growth. That most anti-cancer therapy is directed against the bulk of the tumor, and possibly spares the cancer stem cells, may lie at the heart of treatment failures with conventional modalities. Leukemia stem cells are fairly well described for acute myeloid leukemia (AML), but their existence and relevance for acute lymphoblastic leukemia (...

  17. Acute leukemia in early childhood

    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.

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

    2016-05-19

    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 Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  19. Acute appendicitis caused by acute myeloid leukemia

    Zhang, Shanxiang; Chen, Shaoxiong

    2014-01-01

    Key Clinical Message A case of appendiceal involvement by acute myeloid leukemia (AML) in an adult with recent history of AML transformed from myelodysplastic syndrome (MDS) was presented. Being aware of this rare presentation in particular in a patient with history of MDS and/or AML is important for prompt clinical diagnosis and management.

  20. Clinical Presentations of Acute Leukemia

    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)

  1. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  2. Involvement of Epigenetic Mechanisms in the Regulation of Secreted Phospholipase A2 Expressions in Jurkat Leukemia Cells

    Mario Menschikowski

    2008-11-01

    Full Text Available Epigenetic changes provide a frequent mechanism for transcriptional silencing of genes in cancer cells. We previously established that epigenetic mechanisms are important for control of group IIA phospholipase A2 (PLA2G2A gene transcription in human DU-145 prostate cells. In this study, we analyzed the involvement of such mechanisms in the regulation of five sPLA2 isozymes and the M-type receptor of sPLA2 (sPLA2-R in human leukemic Jurkat cells. These cells constitutively expressed sPLA2-IB, sPLA2-III, sPLA2-X, and sPLA2-R but not sPLA2-IIA and sPLA2-V. Transcription of sPLA2-IIA and sPLA2-V was, however, detected after exposure of cells to the DNA demethylating agent, 5-aza-2′-deoxycytidine (5-aza-dC. Expression of sPLA2-IIA was further enhanced by additional exposure to interferon-γ and blocked by inhibitors of specificity protein 1, nuclear factor κB, and Janus kinase/signal transducer and activator of transcription-dependent pathways. Sequence analysis and methylation-specific polymerase chain reaction of bisulfite-modified genomic DNA revealed two 5′-CpG sites (-111 and -82 in the sPLA2-IIA proximal promoter that were demethylated after 5-aza-dC treatment. These sites may be involved in the DNA binding of specificity protein 1 and other transcription factors. Similar findings after treatment of human U937 leukemia cells with 5-aza-dC indicate that this mechanism of PLA2G2A gene silencing is not restricted to Jurkat and DU-145 cells. These data establish that regulation of sPLA2-IIA and sPLA2-V in Jurkat and other cells involves epigenetic silencing by DNA hypermethylation.

  3. Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

    Dorantes-Acosta, Elisa; Arreguin-Gonzalez, Farina; Rodriguez-Osorio, Carlos A; Sadowinski, Stanislaw; Pelayo, Rosana; Medina-Sanson, Aurora

    2009-01-01

    Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage a...

  4. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  5. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  6. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    ... of WBC) are produced, a child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood leukemia, affecting about 75% of kids with this cancer of the blood cells. Kids ... (AML) Chronic Myelogenous Leukemia (CML) Cancer ...

  7. Epidemiology of acute lymphoblastic leukemia

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury

  8. Acute Myeloid Leukemia Presenting as Acute Appendicitis

    Sherri Rauenzahn

    2013-01-01

    Full Text Available Appendicitis in leukemic patients is uncommon but associated with increased mortality. Additionally, leukemic cell infiltration of the appendix is extremely rare. While appendectomy is the treatment of choice for these patients, diagnosis and management of leukemia have a greater impact on remission and survival. A 59-year-old Caucasian female was admitted to the surgical service with acute right lower quadrant pain, nausea, and anorexia. She was noted to have leukocytosis, anemia, and thrombocytopenia. Abdominal imaging demonstrated appendicitis with retroperitoneal and mesenteric lymphadenopathy for which she underwent laparoscopic appendectomy. Peripheral smear, bone marrow biopsy, and surgical pathology of the appendix demonstrated acute myeloid leukemia (AML with nonsuppurative appendicitis. In the setting of AML, prior cases described the development of appendicitis with active chemotherapy. Of these cases, less than ten patients had leukemic infiltration of the appendix, leading to leukostasis and nonsuppurative appendicitis. Acute appendicitis with leukemic infiltration as the initial manifestation of AML has only been described in two other cases in the literature with an average associated morbidity of 32.6 days. The prompt management in this case of appendicitis and AML resulted in an overall survival of 185 days.

  9. Congenital acute lymphocytic leukemia associated with hyperleucocytic leukemia syndrome

    A two-month-old female infant had congenital acute lymphocytic leukemia 39 days after birth. Cranial CT showed many small high dense spots over the whole brain. The mechanism of occurrence of central neurologic symptoms and the association of hyperleucocytic leukemia are discussed with a review of the literature. (Namekawa, K.)

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

    2013-07-03

    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

  11. Acute Leukemia: Diagnosis, Management, and Potential for Cure

    Stewart, Keith; Keating, Armand

    1988-01-01

    Acute leukemia is an uncommon malignant disorder resulting from the clonal proliferation of hematopoietic precursors of the myeloid or lymphoid lineages. Of the two major subgroups, acute lymphoblastic leukemia is more common in children, while acute myelogenous leukemia predominates in adults. With modern chemotherapy 60%-70% of all children with acute lymphoblastic leukemia can be long-term survivors and are potentially cured. Although the prognosis in acute myelogenous leukemia is less fav...

  12. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Olfa Kassar

    2015-01-01

    Full Text Available Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients.

  13. The distinct role of guanine nucleotide exchange factor Vav1 in Bcl-2 transcription and apoptosis inhibition in Jurkat leukemia T cells

    Jie YIN; Ya-juan WAN; Shi-yang LI; Ming-juan DU; Cui-zhu ZHANG; Xing-long ZHOU; You-jia CAO

    2011-01-01

    Aim: To investigate a novel function of proto-oncogene Vavl in the apoptosis of human leukemia Jurkat cells.Methods: Jurkat cells,Jurkat-derived vavl-null cells(J.Vavl)and Vavl-reconstituted J.WT cells were treated with a Fas agonist antibody,IgM clone CH11.Apoptosis was determined using propidium iodide(PI)staining,Annexin-V staining,DNA fragmentation,cleavage of caspase 3/caspase 8,and poly(ADP-ribose)polymerase(PARP).Mitochondria transmembrane potential(Δψm)was measured using DiOC6(3)staining.Transcription and expression of the Bcl-2 family of proteins were evaluated using semi-quantitative RT-PCR and Western blot,respectively.Bcl-2 promoter activity was analyzed using luciferase reporter assays.Results: Cells lacking Vav1 were more sensitive to Fas-mediated apoptosis than Jurkat and J.WT cells.J.Vav1 cells lost mitochondria transmembrane potential(Δψm)more rapidly upon Fas induction.These phenotypes could be rescued by re-expression of Vav1 in J.Vav1 cells.The expression of Vav1 increased the transcription of pro-survival Bcl-2.The guanine nucleotide exchange activity of Vav1was required for enhancing Bcl-2 promoter activity,and the Vav1 downstream substrate,small GTPase Rac2,was likely involved in the control of Bcl-2 expression.Conclusion: Vav1 protects Jurkat cells from Fas-mediated apoptosis by promoting Bcl-2 transcription through its GEF activity.

  14. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; 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

  15. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    2016-08-10

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Pancytopenia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia

  16. Minimal Residual Disease in Acute Myeloid Leukemia

    Ommen, Hans Beier; Nederby, Line; Toft-Petersen, Marie;

    2014-01-01

    This chapter discusses how minimal residual disease (MRD) is detected and managed in acute myeloid leukemia (AML) patients. The most commonly used techniques to detect residual leukemia in patients in complete remission (CR) are quantitative PCR (qPCR) and multicolor flow cytometry (MFC). While q...

  17. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R.

    2015-01-01

    Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodi...

  18. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... acute lymphocytic leukemia in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

  19. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    2016-03-16

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; 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; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  20. Radioimmunotherapy for Treatment of Acute Leukemia.

    Bodet-Milin, Caroline; Kraeber-Bodéré, Françoise; Eugène, Thomas; Guérard, François; Gaschet, Joëlle; Bailly, Clément; Mougin, Marie; Bourgeois, Mickaël; Faivre-Chauvet, Alain; Chérel, Michel; Chevallier, Patrice

    2016-03-01

    Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID:26897718

  1. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2015-05-05

    Acute Myeloid Leukemia; 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 Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  2. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  3. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. The pan-ErbB tyrosine kinase inhibitor canertinib induces caspase-mediated cell death in human T-cell leukemia (Jurkat) cells

    Trinks, Cecilia, E-mail: Cecilia.trinks@liu.se [Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Severinsson, Emelie A., E-mail: Emelie.severinsson@liu.se [Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Holmlund, Birgitta, E-mail: Birgitta.holmlund@lio.se [Department of Oncology, County Council of Ostergoetland, Linkoeping (Sweden); Green, Anna, E-mail: Anna.green@liu.se [Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Green, Henrik, E-mail: Henrik.green@liu.se [Clinical Pharmacology, Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Joensson, Jan-Ingvar, E-mail: Jan-ingvar.jonsson@liu.se [Experimental Hematology Unit, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Hallbeck, Anna-Lotta, E-mail: Anna-Lotta.Hallbeck@lio.se [Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Department of Oncology, County Council of Ostergoetland, Linkoeping (Sweden); Walz, Thomas M., E-mail: Thomas.Walz@lio.se [Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoeping University, Linkoeping (Sweden); Department of Oncology, County Council of Ostergoetland, Linkoeping (Sweden)

    2011-07-08

    Highlights: {yields} Canertinib induces caspase-mediated apoptosis in T-cell leukemia cells in vitro. {yields} Canertinib mediates activation of the intrinsic apoptotic pathway. {yields} Canertinib induces apoptosis in an ErbB receptor independent manner. {yields} Lymphocyte specific proteins as well as survival kinases are inhibited. {yields} Canertinib may act as a multi-kinase inhibiting drug in human T-cell malignancies. -- Abstract: Canertinib is a novel ErbB-receptor inhibitor currently in clinical development for the treatment of solid tumors overexpressing ErbB-receptors. We have recently demonstrated that canertinib displays anti-proliferative and pro-apoptotic effects in human myeloid leukemia cells devoid of ErbB-receptors. The mechanism mediating these effects are however unknown. In this study, we show that canertinib is able to act as a multi-kinase inhibitor by inhibition of several intracellular kinases involved in T-cell signaling such as Akt, Erk1/2 and Zap-70, and reduced Lck protein expression in the human T-cell leukemia cell line Jurkat. Treatment with canertinib at a concentration of 2 {mu}M caused accumulation of Jurkat cells in the G{sub 1} cell cycle phase and increased doses induced apoptosis in a time-dependent manner. Apoptotic signs of treated cells were detected by Annexin V staining and cleavage of PARP, caspase-3, -8, -9, -10 and Bid. A subset of the pro-apoptotic signals mediated by canertinib could be significantly reduced by specific caspase inhibitors. Taken together, these results demonstrate the dual ability of canertinib to downregulate important signaling pathways and to activate caspase-mediated intrinsic apoptosis pathway in human T-cell leukemia cells.

  5. The pan-ErbB tyrosine kinase inhibitor canertinib induces caspase-mediated cell death in human T-cell leukemia (Jurkat) cells

    Highlights: → Canertinib induces caspase-mediated apoptosis in T-cell leukemia cells in vitro. → Canertinib mediates activation of the intrinsic apoptotic pathway. → Canertinib induces apoptosis in an ErbB receptor independent manner. → Lymphocyte specific proteins as well as survival kinases are inhibited. → Canertinib may act as a multi-kinase inhibiting drug in human T-cell malignancies. -- Abstract: Canertinib is a novel ErbB-receptor inhibitor currently in clinical development for the treatment of solid tumors overexpressing ErbB-receptors. We have recently demonstrated that canertinib displays anti-proliferative and pro-apoptotic effects in human myeloid leukemia cells devoid of ErbB-receptors. The mechanism mediating these effects are however unknown. In this study, we show that canertinib is able to act as a multi-kinase inhibitor by inhibition of several intracellular kinases involved in T-cell signaling such as Akt, Erk1/2 and Zap-70, and reduced Lck protein expression in the human T-cell leukemia cell line Jurkat. Treatment with canertinib at a concentration of 2 μM caused accumulation of Jurkat cells in the G1 cell cycle phase and increased doses induced apoptosis in a time-dependent manner. Apoptotic signs of treated cells were detected by Annexin V staining and cleavage of PARP, caspase-3, -8, -9, -10 and Bid. A subset of the pro-apoptotic signals mediated by canertinib could be significantly reduced by specific caspase inhibitors. Taken together, these results demonstrate the dual ability of canertinib to downregulate important signaling pathways and to activate caspase-mediated intrinsic apoptosis pathway in human T-cell leukemia cells.

  6. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    ... both ALL and acute myeloid leukemia (AML). Japanese atomic bomb survivors had a greatly increased risk of developing ... cell acute lymphocytic leukemia. Most cases occur in Japan and the Caribbean area. This disease is not ...

  7. Do We Know What Causes Acute Myeloid Leukemia?

    ... Topic Can acute myeloid leukemia be prevented? Do we know what causes acute myeloid leukemia? Some people ... genes – the instructions for how our cells function. We tend to look like our parents because they ...

  8. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    ... treatment for acute lymphocytic leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is ... with your doctor. You should feel free to ask any question that’s on your mind, no matter ...

  9. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    2016-02-12

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  10. Psychological Risk Factors in Acute Leukemia

    Gouva M.

    2009-04-01

    Full Text Available Several theoretical models have been occasionally proposed to account for the involvement of psychological factors in cancer genesis. Family environment and relations as well as certain personality traits were correlated to cancer onset. However, little is known in the case of acute leukemia. The present study examined family environment, state-trait anxiety, hostility and the direction of hostility as well as alexithymia in 41 acute leukemia patients and their first degree relatives (70. In accordance with previous findings, the present results showed that family cohesion, conflict and organization as well as guilt, state anxiety and alexithymia were significant risk factors for the development of the disease.

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

    2016-04-21

    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

  12. Evaluation of RT-PCR to Detect Translocations in Children Diagnosed with Acute Lymphoblastic Leukemia

    H Galehdari

    2009-12-01

    Full Text Available "nBackground: Acute lymphoblastic leukemia (ALL is the most common subtype of childhood cancer. Chromosomal ab­normality, specially the replacement of chromosomal material is one of the main reasons in generating leukemia, wherein the kind of translocation play a key role in managing the remedy. The goal of the present study was to develop a reliable, rapid, and cost effective method to detect translocations, which are the main sources of leukemia."nMethods: Twenty seven samples were collected from leukemia affected individuals that were referred to the Shafa Hospital in Ahwaz from summer 2007 to spring2008. Total RNA was extracted from one milliliter whole blood, and then reversely tran­scribed using reverse transcriptase. Finally, multiplex RT-PCR was performed for each sample."nResults: Cell lines (K562, Jurkat E 6.1 that are harboring known translocations were used as positive control, with addi­tional internal control to prove false negative results. Translocations t (9; 22, t (12; 21, t (1; 19 and t (4; 11 were ob­served in patients that have been diagnosed with the ALL, respectively. No Translocation has been seen in individuals suf­fering lymphoma."nConclusion: Multiplex RT-PCR assay is an effective, sensitive, accurate, and cost-effective diagnostic tool, which can im­prove the ability to accurately and rapidly risk-stratify patients that were diagnosed with acute lymphoblastic leukemia.

  13. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    2015-07-20

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  14. The effect of gallic acid on Jurkat cell line

    Sourani Zahra

    2015-10-01

    Full Text Available Introduction: Acute lymphoblastic leukemia (ALL is the most prevalent leukemia in children. Fruits and plants have a wide range of biological functions including anti-proliferative effect. Gallic acid (GA, is a polyhydroxyphenolic compound that is widely distributed in the natural plants. The aim of the present study was the evaluation of the effect of GA on proliferation inhibition of Jurkat cells, the lymphoblastic leukemia cell line. Methods: Jurkat cell line was cultured in blood cells culture media in a standard conditions with different concentrations of GA (0-100 μm for 24, 48 and 72 hours. The effect of GA on cell viability was measured using MTS assay. Results: Decline of cell viability to less than 50% was observed at 60, 50 and 30 μm concentrations after 24, 48 and 72 hours incubation time, respectively. Conclusion: The results demonstrated that the polyphenolic compound, GA with antioxidant capability is effective in proliferation inhibition in Jurkat lymphoblastic leukemia cell line with a time and dose dependent manner. Therefore, GA may be a potential compound for cancer prevention and treatment.

  15. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    2016-08-10

    Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

  16. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; 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); Recurrent Adult Acute Myeloid Leukemia

  17. Bilateral breast involvement in acute myeloid leukemia

    Hakeem A, Mandakini BT, Asif K, Firdaus, Shagufta RC

    2013-04-01

    Full Text Available Breast involvement by leukemic infiltration is usually bilateral, but may be unilateral. Clinically patients can present with either single or multiple masses, or with diffuse breast engorgement, with or without nodularity. The affected patients are predominantly young adults. We present a case of an adolescent girl with acute myeloid leukemia having bilateral breast infiltration by leukemic cells.

  18. P-GLYCOPROTEIN QUANTITATION IN ACUTE LEUKEMIA

    Mali in Nikougoftar

    2003-06-01

    Full Text Available Multi drug resistance(MDR is a major problem in the treatment of cancer and hemalological malignancies. This resistance is multi factorial and is the result of decreased intra cellular drug accumulation. This is partly due to the presence of a 170KD intra membranous protein termed P-glycoprotein(P-gp that is an energy-dependent efflux pump which has increased expression on drug-resistance cells. In this study we identified the presence of P-gp by staining with Fluorescent Iso Thio Cyanate (FITC conjugated anti P-gp in acute leukemia patients and flow cytometry in addition to performing immunophenotype analysis and French, American British (FAB classification. Results revealed that one fifth of leuke¬mic patients expressed P-gp and this phenotype was more prevalent in Acute Undifferentiated Leukemia(AUL and Acute Myelogenous Leukemia (AML than in Acute Lymphoblastic Leukemia(ALL. Other findings showed a logical rela¬tionship between this phenotype and age groups. There was not any association between P-gp+ phenotype and FAB and Immunophenotyping sub classification, but there was a linear relationship between CD34 and CD7 expression and P-gp+ phenotype. The accumulation of P-gp molecule that was stated as Mean Fluores¬cence Intensity (MFI on the blasts1 membrane of AUL and AML patients showed marked increase in comparison to ALL. Furthermore MFI in P-gp+ relapsed patients was much more than P-gp+ pretreatment patients.

  19. Use of clofarabine for acute childhood leukemia

    A Pession

    2010-06-01

    Full Text Available A Pession, R Masetti, K Kleinschmidt, A MartoniPediatric Oncology and Hematology “Lalla Seràgnoli”, University of Bologna, ItalyAbstract: A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols.Keywords: clofarabine, pediatric acute lymphoblastic leukemia, pediatric acute myeloid leukemia

  20. Molecular Insights in MLL Rearranged Acute Leukemia

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  1. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2013-09-13

    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

  2. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    2016-02-22

    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); 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 Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  3. Differentiation Therapy of Acute Myeloid Leukemia

    Elzbieta Gocek

    2011-05-01

    Full Text Available 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 D3 (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.

  4. Differentiation Therapy of Acute Myeloid Leukemia

    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 D3 (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

  5. Differentiation Therapy of Acute Myeloid Leukemia

    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.

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

    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

  7. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2015-10-19

    Adult Acute Megakaryoblastic Leukemia (M7); 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

  8. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    Chen YJ

    2016-07-01

    Full Text Available Yu-Jen Chen,1–4 Li-Wen Fang,5 Wen-Chi Su,6,7 Wen-Yi Hsu,1 Kai-Chien Yang,1 Huey-Lan Huang8 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Nutrition, I-Shou University, Kaohsiung, 6Research Center for Emerging Viruses, China Medical University Hospital, 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 8Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan, Republic of China Abstract: Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML, chronic myeloid leukemia (CML, and acute lymphoblastic leukemia (ALL cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of

  9. Use of clofarabine for acute childhood leukemia

    Masetti, Riccardo

    2010-01-01

    A Pession, R Masetti, K Kleinschmidt, A MartoniPediatric Oncology and Hematology “Lalla Seràgnoli”, University of Bologna, ItalyAbstract: A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity i...

  10. Systemic mastocytosis with associated acute myelogenous leukemia

    Zhrebker, Leah; Cooper, Barry; Krause, John R.

    2014-01-01

    Systemic mastocytosis (SM) is a condition associated with a clonal neoplastic proliferation of mast cells. Approximately 40% of patients with SM present with an associated clonal hematological non–mast cell lineage disorder. Patients presenting with SM–acute myeloid leukemia (AML) have the worst prognosis. We present a case of a 62-year-old woman who was diagnosed with SM-AML. After initial treatment with a standard regimen of cytosine arabinoside (Ara-C)/idarubicin, her bone marrow showed re...

  11. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    Fullmer, Amber; O’Brien, Susan; Kantarjian, Hagop; Jabbour, Elias

    2009-01-01

    The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to availabl...

  12. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in...

  13. Cytogenetic studies of Acute Myeloid Leukemia

    Tarek Abd -Alla Atia

    2010-01-01

    Acute myeloid leukemia (AML) describes as a group of hematopoietic stem cell disorders characterized by expansion of undifferentiated myeloid progenitors. Acquired chromosomal anomaly particularly reciprocal translocations constitute one of the major events contribute to leukemogenesis. Patient and Methods: 45 untreated, newly diagnosed patients with de novo AML were enrolled in the present study and subjected to cytogenetic analysis. Four ml of heparinized peripheral blood were collected for...

  14. Pathogenesis and prognostication in acute lymphoblastic leukemia

    Zuckerman, Tsila; Rowe, Jacob M.

    2014-01-01

    The process of lymphoid maturation is tightly controlled by the hierarchical activation of transcription factors and selection through functional signal transduction. Acute lymphoblastic leukemia (ALL) represents a group of B/T-precursor-stage lymphoid cell malignancies arising from genetic alterations that block lymphoid differentiation and drive aberrant cell proliferation and survival. With recent advances in next-generation sequencing, we are discovering new mutations affecting normal lym...

  15. Frank hematuria as the presentation feature of acute leukemia

    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.

  16. Expression of CD133 in acute leukemia.

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients. PMID:23532815

  17. Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

    Zeng, Dong-Feng [Department of Hematology, XinQiao Hospital, Third Military Medical University, ChongQing (China); Liu, Ting [Department of Ophthalmology, DaPing Hospital, Third Military Medical University, ChongQing (China); Chang, Cheng; Zhang, Xi; Liang, Xue; Chen, Xing-Hua; Kong, Pei-Yan [Department of Hematology, XinQiao Hospital, Third Military Medical University, ChongQing (China)

    2012-06-29

    Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenvironment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1α secreted by stromal cells was decreased. When HIF-1α was blocked, the co-cultured Jurkat cell's adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

  18. Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

    Zeng Dong-Feng

    2012-10-01

    Full Text Available Hypoxia inducible factor-1α (HIF-1α is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF and stromal cell-derived factor-1α (SDF-1α were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell’s adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

  19. Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

    Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenvironment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1α secreted by stromal cells was decreased. When HIF-1α was blocked, the co-cultured Jurkat cell's adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs

  20. Systemic mastocytosis with acute myelomonocytic leukemia: a case report

    Kar, Rakhee; Rao, Seema; Pati, Hara Prasad

    2008-01-01

    Bone marrow mastocytosis may be associated with many clonal non mast cell hematological neoplasms and its association with acute myeloid leukemia especially with t (8; 21) has been described. We describe an interesting case of coexistence of systemic mastocytosis with acute myelomonocytic leukemia in a young child. Diagnosis of acute myelomonocytic leukemia was based on bone marrow aspirate findings coupled with cytochemistry. Systemic mastocytosis was diagnosed on the basis of bone marrow bi...

  1. Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

    de Rooij, Jasmijn D.E.; Beuling, Eva; Marry M van den Heuvel-Eibrink; Obulkasim, Askar; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Sonneveld, Edwin; Gibson, Brenda E.S.; Pieters, Rob; Zimmermann, Martin; Zwaan, C. Michel; Fornerod, Maarten

    2015-01-01

    IKAROS family zinc finger 1/IKZF1 is a transcription factor important in lymphoid differentiation, and a known tumor suppressor in acute lymphoid leukemia. Recent studies suggest that IKZF1 is also involved in myeloid differentiation. To investigate whether IKZF1 deletions also play a role in pediatric acute myeloid leukemia, we screened a panel of pediatric acute myeloid leukemia samples for deletions of the IKZF1 locus using multiplex ligation-dependent probe amplification and for mutations...

  2. Growth Inhibition and Apoptosis Due to Restoration of E2A Activity in T Cell Acute Lymphoblastic Leukemia Cells

    Park, Steven T.; Nolan, Garry P.; Sun, Xiao-Hong

    1999-01-01

    Two models have been proposed for the molecular mechanism by which the Tal1 oncogene causes T cell acute lymphoblastic leukemia (T-ALL). The activation model suggests that Tal1 as heterodimers with the E2A transcription factor activates the expression of oncogenes. The inhibition model postulates that Tal1 interferes with the tumor-suppressing function of E2A. In the Jurkat T cell line, originally derived from a patient with T-ALL, Tal1 is complexed with E2A proteins and the transcriptional a...

  3. Leukemia.

    Juliusson, Gunnar; Hough, Rachael

    2016-01-01

    Leukemias are a group of life threatening malignant disorders of the blood and bone marrow. In the adolescent and young adult (AYA) population, the acute leukemias are most prevalent, with chronic myeloid leukemia being infrequently seen. Factors associated with more aggressive disease biology tend to increase in frequency with increasing age, whilst tolerability of treatment strategies decreases. There are also challenges regarding the effective delivery of therapy specific to the AYA group, consequences on the unique psychosocial needs of this age group, including compliance. This chapter reviews the current status of epidemiology, pathophysiology, treatment strategies and outcomes of AYA leukemia, with a focus on acute lymphoblastic leukemia and acute myeloid leukemia. PMID:27595359

  4. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2016-01-07

    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; Secondary Acute Myeloid Leukemia

  5. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia or Acute Leukemia in Remission

    2016-06-09

    Adult Acute Lymphoblastic Leukemia in Remission; 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); Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

  6. Criteria and Classification of Hybrid Acute Leukemia in 72 Acute Leukemias Based Mainly on Flow Cytometric Analysis

    Aoki, Sadao; Nomoto, Nobuhiko; Maruyama, Souichi; Shinada, Shoji; Shibata, Akira

    1991-01-01

    Phenotypes of leukemic cells can be determined through dual staining with pairs of FITC-labeled and PE-labeled monoclonal antibodies using a laser flow cytometer. Hybrid acute leukemia (HAL) was diagnosed when leukemic cells expressed 2 or more lymphoid markers and at least on myeloid marker simultaneously. Based on this criteria, nineteen out of 72 cases with untreated acute leukemia were diagnosed as HAL, 15 of 29 (51%) patients with acute lymphoblastic leukemia and 4 of 43 (9%) patients wi...

  7. Acute nonlymphocytic leukemia following bladder instillations with thiotepa.

    Easton, D. J.; Poon, M. A.

    1983-01-01

    A case of therapy-related leukemia is described. Other cases of acute nonlymphocytic leukemia have been associated with the intramuscular administration of thiotepa (an alkylating agent), but this patient received only intravesical instillations of the drug. The interval between the start of chemotherapy and the onset of leukemia was 56 months.

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

    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.

  9. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia.

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; Deryckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  10. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities

  11. The genetic signature of acute leukemia in infacy

    Chantrain, Christophe; Poirel, Hélène

    2010-01-01

    Infant leukemia is a rare malignant disease with clinical and biological features distinct from older children. It is characterized by a high incidence of mixed lineage leukemia (MLL) gene rearrangement and a poor outcome despite intensive chemotherapy. Recent genetic studies argue in favor of a unique biology of infant acute leukemia. This review describes the specific genetic signature of infant leukemia. It discusses the important insights it provides into the understanding of leukemogenes...

  12. Retinoid Differentiation Therapy for Common Types of Acute Myeloid Leukemia

    Philip Hughes; Geoffrey Brown

    2012-01-01

    Many cancers arise in a tissue stem cell, and cell differentiation is impaired resulting in an accumulation of immature cells. The introduction of all-trans retinoic acid (ATRA) in 1987 to treat acute promyelocytic leukemia (APL), a rare subtype of acute myeloid leukemia (AML), pioneered a new approach to obtain remission in malignancies by restoring the terminal maturation of leukemia cells resulting in these cells having a limited lifespan. Differentiation therapy also offers the prospect o...

  13. Data quality in the Danish National Acute Leukemia Registry

    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....

  14. Skin changes in acute myelogenous leukemia

    Mittal R

    2000-01-01

    Full Text Available A 65-year old woman developed progressive, firm, mild to moderately itchy, erythematous, papular and nodular lesions, over cheeks, extensors of limbs, scalp and lower back without any accompanying systemic complaints except for severe backache. Initially clinical diagnosis was cutaneous sarcoidosis. However presence of myeloblasts, monoblasts, myelocytes and metamyelocytes in peripheral blood smear and typical histopathology of nodule with mixed cellular infiltrate more around blood vessels, sweat glands and hair follicles with admixture of larger polymorphonuclears (myeloblasts/myelocytes, eosinophils with double nuclei, and larger phagocytic cells confirmed the diagnosis of acute myelogenous leukemia (AML.

  15. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Sabina Chiaretti

    2014-10-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly in function of ALL subset, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review offers a glimpse on how best identify ALL and the most relevant ALL subsets.

  16. Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    2016-04-26

    B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B Lymphoblastic Lymphoma; Recurrent T Lymphoblastic Leukemia/Lymphoma; Refractory B Lymphoblastic Lymphoma; Refractory T Lymphoblastic Lymphoma; T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

  17. Perinatal risk factors for acute myeloid leukemia.

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2015-12-01

    Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML. PMID:26113060

  18. How Is Acute Myeloid Leukemia Classified?

    ... also form the basis for treating these leukemias. Markers on the leukemia cells If the leukemia cells ... no signs or symptoms of the disease. A molecular complete remission means there is no evidence of ...

  19. Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT.

    Ishiyama, Ken; Yamaguchi, Takuhiro; Eto, Tetsuya; Ohashi, Kazuteru; Uchida, Naoyuki; Kanamori, Heiwa; Fukuda, Takahiro; Miyamura, Koichi; Inoue, Yoshiko; Taguchi, Jun; Mori, Takehiko; Iwato, Koji; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Sakamaki, Hisashi; Takami, Akiyoshi

    2016-08-01

    Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. PMID:27244257

  20. A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines

    Altenburg, Jeffrey D.; Harvey, Kevin A.; McCray, Sharon; Xu, Zhidong [Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org [Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Biology, Indiana University-Purdue University, Indianapolis, IN (United States); Department of Medicine, Indiana University School of Medicine, Indianapolis, IN (United States)

    2011-07-29

    Highlights: {yields} 2,6-Diisopropylphenyl-docosahexaenoamide conjugates (DIP-DHA) inhibits the proliferation of T-cell leukemic cell lines. {yields} DIP-DHA resulted in increased activation of caspase-3, and caspase-7. {yields} DIP-DHA significantly downregulated CXCR4 surface expression. -- Abstract: We have previously characterized the effects of 2,6-diisopropylphenyl-docosahexaenoamide (DIP-DHA) conjugates and their analogs on the proliferation and progression of breast cancer cell lines. For this study, we investigated the effects of the DIP-DHA conjugate on 2 representative T cell acute lymphoblastic leukemia (T-ALL) cell lines: CEM and Jurkat. Treatment of both cell lines with DIP-DHA resulted in significantly greater inhibition of proliferation and induction of apoptosis than that of parent compounds, 2,6-diisopropylphenol (DIP) or docosahexaenoate (DHA). Treatment of the cells with DIP-DHA resulted in increased activation of caspase-3, and caspase-7. Furthermore, induction of apoptosis in both cell lines was reversed in the presence of a caspase family inhibitor. Treatment with DIP-DHA reduced mitochondrial membrane potential. These observations suggest that the effects are driven by intrinsic apoptotic pathways. DIP-DHA treatment also downregulated surface CXCR4 expression, an important chemokine receptor involved in cancer metastasis that is highly expressed in both CEM and Jurkat cells. In conclusion, our data suggest that the DIP-DHA conjugate exhibits significantly more potent effects on CEM and Jurkat cells than that of DIP or DHA alone. These conjugates have potential use for treatment of patients with T cell acute lymphoblastic leukemia.

  1. A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines

    Highlights: → 2,6-Diisopropylphenyl-docosahexaenoamide conjugates (DIP-DHA) inhibits the proliferation of T-cell leukemic cell lines. → DIP-DHA resulted in increased activation of caspase-3, and caspase-7. → DIP-DHA significantly downregulated CXCR4 surface expression. -- Abstract: We have previously characterized the effects of 2,6-diisopropylphenyl-docosahexaenoamide (DIP-DHA) conjugates and their analogs on the proliferation and progression of breast cancer cell lines. For this study, we investigated the effects of the DIP-DHA conjugate on 2 representative T cell acute lymphoblastic leukemia (T-ALL) cell lines: CEM and Jurkat. Treatment of both cell lines with DIP-DHA resulted in significantly greater inhibition of proliferation and induction of apoptosis than that of parent compounds, 2,6-diisopropylphenol (DIP) or docosahexaenoate (DHA). Treatment of the cells with DIP-DHA resulted in increased activation of caspase-3, and caspase-7. Furthermore, induction of apoptosis in both cell lines was reversed in the presence of a caspase family inhibitor. Treatment with DIP-DHA reduced mitochondrial membrane potential. These observations suggest that the effects are driven by intrinsic apoptotic pathways. DIP-DHA treatment also downregulated surface CXCR4 expression, an important chemokine receptor involved in cancer metastasis that is highly expressed in both CEM and Jurkat cells. In conclusion, our data suggest that the DIP-DHA conjugate exhibits significantly more potent effects on CEM and Jurkat cells than that of DIP or DHA alone. These conjugates have potential use for treatment of patients with T cell acute lymphoblastic leukemia.

  2. Age Difference in Immunophenotype of Acute Leukemia

    Kazunori Nakase

    2006-01-01

    Full Text Available We examined the immunophenotype of 880 cases with acute leukemia and analyzed their age difference in relation to the morphological subtype and the karyotype. We divided the patients into 3 age groups: child (0-15 years, adult (16-59 years and elderly (60 years and older group. The diagnoses based on the French-American-British (FAB criteria and the immunophenotype as follows: 453 patients as acute myeloid leukemia (AML, 366 as precursor B-cell acute lymphoblastic leukemia (ALL (24 CD10- cases and 342 CD10+ cases, 10 B-cell ALL and 51 T-cell ALL. In AML, there were no significant age differences in the frequency of FAB subtypes. Karyotypically, the frequencies of t(8;21 and 11q23 decreased with age and that of 5/7/8 abnormality increased with age. As for the immunophenotype in each FAB subtype, CD11b in M2 (0% and CD34 in M3 (0% were less commonly expressed in the child group than in the other age groups. Whereas Both CD11b (100% and CD34 (60% in M4 were more predominantly expressed in the child group than in the other age groups. Lymphoid antigen, CD19 showed a higher frequency (38.5% in the child M2 than did other age M2 groups, reflecting the distribution pattern of t(8;21 among the 3 age groups. Additionally, the child group more frequently expressed this antigen (33.3% than the older groups among CD7+ AML. In ALL, the frequency of CD10+ precursor B ALL was more common in the child group (84% than in the adult group. On the other hand, B-cell ALL showed a lower frequency (0.7% in the child group and T-cell ALL did a higher frequency (18.3% in the adult group than any other age groups, respectively. Although the frequency of t(9;22 increased with age in CD10+ precursor-B ALL, myeloid antigen (CD13/CD33 expression evenly distributed among the 3 age groups. Our results suggest that phenotypic heterogeneity gradually emerged with age irrespective of the pattern of karyotype.

  3. 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

    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

  4. Role of autophagy in acute myeloid leukemia therapy

    Su-Ping Zhang; Yu-Na Niu; Na Yuan; Ai-Hong Zhang; Dan Chao; Qiu-Ping Xu; Li-Jun Wang

    2013-01-01

    Despite its dual role in determining cell fate in a wide array of solid cancer cell lines,autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis.However,autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein,though the molecular mechanism remains elusive.Nevertheless,since it can induce cooperation with apoptosis and differentiation in response to autophagic signals,autophagy can be manipulated for a better therapy on acute myeloid leukemia.

  5. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan;

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...... development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia....

  6. Cranial computerized tomography in children suffering from acute leukemia

    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)

  7. Prethymic Cytoplasmic CD3 Negative Acute Lymphoblastic Leukemia or Acute Undifferentiated Leukemia: A Case Report

    Elisa Cannizzo

    2011-01-01

    Full Text Available Acute undiffentiated leukemia (AUL is an acute leukemia with no more than one membrane marker of any given lineage. Blasts often express HLA-DR, CD34, and/or CD38 and may be positive for terminal deoxynucleotidyl transferase (TdT. The expression of CD34, HLA-DR, and CD38 has been shown in pro-T-ALL, although in this case, blasts should also express CD7 and cyCD3. However, some cases of T-ALL without CD3 in the cytoplasm and all TCR chain genes in germ line configuration are reported, features that fit well with a very early hematopoietic cell. We report a case of acute leukemia CD34+/−HLADR+CD7+CD38+cyCD3− in which a diagnosis of AUL was considered. However the blasts were also positive for CD99 and TCR delta gene rearrangement which was found on molecular studies. Therefore a differential diagnosis between AUL and an early cyCD3 negative T-ALL was debated.

  8. Minimal residual disease in acute lymphoblastic leukemia.

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well demonstrated; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and to estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD and the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help to clarify the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  9. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  10. Mixed Phenotypic Acute Leukemia Presenting as Mediastinal Mass-2 Cases.

    Vardhan, Rig; Kotwal, Jyoti; Ganguli, Prosenjit; Ahmed, Rehan; Sharma, Ajay; Singh, Jasjit

    2016-06-01

    Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months. We wish to present two cases of mixed phenotypic acute leukemia who presented with mediastinal masses, were suspected to be T cell lymphoma/leukemia clinically and radiologically. In one case, tissue diagnosis was given as lymphoma for which treatment was given. These cases show that patients diagnosed as lymphoma on histopathology can be cases of mixed phenotype acute leukemia and varying specific treatment protocols and follow up are required. Awareness of these entities will help in proper diagnosis and treatment. PMID:27408360

  11. Molecular mechanisms in differentiation-induction in acute promyelocytic leukemia

    Nigten, Jeannet

    2007-01-01

    Leukemia is a hematological malignancy that is characterized by the clonal expansion of immature hematopoietic cells, which have escaped from the tightly coordinated cell cycle regulation, differentiation and apoptosis controls. In general, leukemia is characterized by a variety of mutations in pathways that are required for normal hematopoiesis. This thesis describes target genes of the mutated transcription factor PML-RAR , which is expressed in acute promyelocytic leukemia (APL) cells. APL...

  12. The MLL recombinome of acute leukemias in 2013

    Meyer, C; Hofmann, Julian; Burmeister, T;

    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...

  13. MOLECULAR PATHOGENESIS OF SECONDARY ACUTE PROMYELOCYTIC LEUKEMIA

    Neil Osheroff

    2011-01-01

    Full Text Available

    Balanced chromosomal translocations that generate chimeric oncoproteins are considered to be initiating lesions in the pathogenesis of acute myeloid leukemia. The most frequent is the t(15;17(q22;q21, which fuses the PML and RARA genes, giving rise to acute promyelocytic leukemia (APL. An increasing proportion of APL cases are therapy-related (t-APL, which develop following exposure to radiotherapy and/or chemotherapeutic agents that target DNA topoisomerase II (topoII, particularly mitoxantrone and epirubicin. To gain insights into molecular mechanisms underlying the formation of the t(15;17 we mapped the translocation breakpoints in a series of t-APLs, which revealed significant clustering according the nature of the drug exposure. Remarkably, in approximately half of t-APL cases arising following mitoxantrone treatment for breast carcinoma or multiple sclerosis, the chromosome 15 breakpoint fell within an 8-bp “hotspot” region in PML intron 6, which was confirmed to be a preferential site of topoII-mediated DNA cleavage induced by mitoxantrone.  Chromosome 15 breakpoints falling outside the “hotspot”, and the corresponding RARA breakpoints were also shown to be functional topoII cleavage sites. The observation that particular regions of the PML and RARA loci are susceptible to topoII-mediated DNA damage induced by epirubicin and mitoxantrone may underlie the propensity of these agents to cause APL.

     

  14. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    2014-04-03

    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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia

    Degryse, Sandrine; Cools, Jan

    2015-01-01

    Recent studies of acute lymphoblastic leukemia have identified activating mutations in components of the interleukin-7 receptor complex (IL7R, JAK1, and JAK3). It will be of interest to investigate both JAK1 and JAK3 kinase inhibitors as targeted agents for these leukemias.

  16. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    2015-02-24

    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(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; Untreated Adult Acute Myeloid Leukemia

  17. Signaling pathways involved in apoptosis induced by novel angucycline antibiotic landomycin E in Jurkat T leukemia cells

    Panchuk R. R.

    2011-04-01

    Full Text Available Aim. To study the molecular mechanisms of action of novel anticancer antibiotic landomycin E (LE. Methods. Annexin V/propidium iodide, DAPI (4',6-diamidino-2-phenylindole staining, Western-blot analysis. Results. LE applied in 2 µg/ml dose (IC50, induced reactive oxygen species (ROS-dependent splitting of poly [ADP-ribose] polymerase 1 (PARP-1 and DNA Fragmentation Factor 45 (DFF45 proteins involved in DNA reparation. This effect was observed 6 h after the start of treatment and it positively correlated with phosphatidyl serine externalization (early morphological marker of apoptosis. We suggest that cleavage of PARP-1 and DFF45 was mediated by active caspase-7 which is a key effector caspase in the LE-induced apoptosis in leukemia cells. We found that activation of initiator procaspase-10 (involved in receptor- mediated apoptosis was the earliest detected event in LE-induced apoptotic signaling pathways; however, this activation was shown to be ROS-independent. We also demonstrated that the induction of apoptosis by LE is accompanied by activation of apoptosis-inducing factor (AIF in mitochondria. Conclusions. Our data suggest that LE-induced cascade of apoptotic events is started by the initiator caspase-10 which leads to activation of the effector caspase-7 and AIF that is known to induce caspase-independent apoptosis involving ROS generation.

  18. Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

    Ibrahim Bayram

    2014-01-01

    In children patients with acute lymphoblastic leukemia, according to the European bone marrow transplant handbook, the indications for stem cell transplantation, conditioning regimen, donor selection and information about sources of stem cells will be evaluated.

  19. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M. Iqbal; Rahman, Atta-ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using 1H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  20. Advances in Management of Acute Promyelocytic Leukemia with Arsenic Trioxide

    MA Jun

    2007-01-01

    @@ Acute promyelocytic leukemia (APL), with specific features in cell morphology, is classified as M3 by French-American-British (FAB).Among M3, 95% of patients show specific chromosome translocation t(15;17)q(22;21) with PML-RAR α fusion gene, and 5% of patients show other subtypes. According to the statistical analysis of 2 540 adult acute myeloid leukemia (AML)cases in Harbin Institute of Hematology & Oncology, APL accounted for 23%.

  1. Epigenetic regulators as promising therapeutic targets in acute myeloid leukemia

    Gallipoli, Paolo; Giotopoulos, George; Huntly, Brian J. P.

    2015-01-01

    Acute myeloid leukemia (AML), the most prevalent acute leukemia in adults, is an aggressive hematological malignancy arising in hematopoietic stem and progenitor cells. With the exception of a few specific AML subtypes, the mainstays of treatment have not significantly changed over the last 20 years, and are still based on standard cytotoxic chemotherapy. As a result, clinical outcome remains poor for the majority of patients, with overall long-term survival in the region of 20?30%. Recent su...

  2. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    2014-08-13

    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(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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

    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.

  4. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat.

    Nagata, K.(Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan); Ohtani, K; Nakamura, M.; Sugamura, K

    1989-01-01

    We examined the ability of the trans-acting factor p40tax of human T-cell leukemia virus type I (HTLV-I), which is thought to be a crucial molecule in T-cell transformation by HTLV-I, to activate expression of a set of endogenous cellular genes related to T-cell proliferation. For this purpose we established a subclone (JPX-9) of Jurkat cells that was stably transfected with an expression plasmid containing the p40tax gene, whose expression is definitely dependent on heavy-metal ions. Express...

  5. PML-RARα co-operates with Sox4 in acute myeloid leukemia development in mice

    Omidvar, Nader; Maunakea, Mei Lin; Jones, Letetia; Sevcikova, Sabina; Yin, Bin; Himmel, Karen L.; Tennant, Thelma R.; Le Beau, Michelle M; Largaespada, David A.; Kogan, Scott C.

    2013-01-01

    Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. To identify co-operating pathways to leukemogenesis, we crossed MRP8-PML/RARA transgenic mice with BXH-2 mice which harbor an endogenous murine leukemia virus that causes acute myeloid leukemia. Approximately half of the leukemias that arose in this cross showed features of acute promyelocytic leukemia. We identified 22 proviral insertion sites in acute promyelocytic-l...

  6. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia

    Levine, Ross L.; Loriaux, Marc; Huntly, Brian J. P.; Loh, Mignon L.; Beran, Miroslav; Stoffregen, Eric; Berger, Roland; Clark, Jennifer J.; Willis, Stephanie G.; Nguyen, Kim T.; Flores, Nikki J.; Estey, Elihu; Gattermann, Norbert; Armstrong, Scott; Look, A. Thomas; Griffin, James D.; Bernard, Olivier A.; Heinrich, Michael C.; Gilliland, D. Gary; Druker, Brian; Deininger, Michael W. N.

    2005-01-01

    Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML)/atypical chronic myelogenous leukemia (aCML), myelodysplastic syndrome (MDS), B-lineage acute lymphoblastic leukemia (ALL), T-cell ALL, and chronic lymphocytic leukemia (CLL). Analysis of 222 patients with AML identified JAK2V617F mutations in 4 patients with AML, 3 of whom had a preceding MPD. JAK2V617F mutations were identified in 9 (7.8%) of 116 CMML/a CML samples, and in 2 (4.2%) of 48 MDS samples. We did not identify the JAK2V617F disease allele in B-lineage ALL (n = 83), T-cell ALL (n = 93), or CLL (n = 45). These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies. PMID:16081687

  7. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  8. PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF SURVIVIN IN ACUTE LEUKEMIA

    王晓娟; 戴国仪; 曹利民; 王国华; 朱慧芬; 张悦; 沈关心

    2002-01-01

    Objective: To investigate the expression of survivin gene and its significance in acute leukemia. Methods: The expression of surviving in 134 acute leukemia patients and 4 leukemia cell lines was detected by RT-PCR and immunofluorescence analysis. Results: We detected survivin expression in 78 of 134 acute leukemia patients and all the cell lines but not in normal controls and anemia patients. Survivin gene expression correlated with a lower white blood cell count, which was 11×109/L and 48×109/L in the positive and negative group respectively (P<0.01 by the Mann-Whitney test). In 55 cases of FAB M1/M2/M3, it was associated with leukemic cell maturation(P<0.01 by the Fisher test). Survivin expression was strongly related to survival time of acute leukemia patients (P<0.05). Conclusion: These data suggest that survivin expression may be considered as a new unfavorable prognostic factor for acute leukemia due to its important role in apoptosis inhibition that influences disease outcome.

  9. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    2015-08-04

    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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  10. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    2016-04-07

    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 Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  11. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    2014-09-16

    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 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; Untreated Adult Acute Myeloid Leukemia

  12. Acute myeloid leukemia masquerading as hepatocellular carcinoma.

    Abu-Zeinah, Ghaith F; Weisman, Paul; Ganesh, Karuna; Katz, Seth S; Dogan, Ahmet; Abou-Alfa, Ghassan K; Stein, Eytan M; Jarnagin, William; Mauro, Michael J; Harding, James J

    2016-06-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient's liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  13. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    Abu-Zeinah, Ghaith F.; Weisman, Paul; Ganesh, Karuna; Katz, Seth S.; Dogan, Ahmet; Abou-Alfa, Ghassan K.; Stein, Eytan M.; Jarnagin, William; Mauro, Michael J.

    2016-01-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient’s liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  14. Acute myeloid leukemia in the older patient.

    Godwin, John E; Smith, Scott E

    2003-10-15

    Acute myeloid leukemia (AML) is an extremely heterogeneous disorder. The biology of AML is incompletely understood, but much data indicates that older patients have a more biologically diverse and chemotherapy resistant form of AML that is quite different from that seen in the younger patients. Approximately 60% of AML cases are in patients greater than 60 years of age, so the predominant burden is in older patients. This problem will be magnified in the future, because the US population is both growing and aging. When one examines the treatment outcomes of older AML patients over the last three decades, there is little progress in long-term survival. Nine major published randomized placebo controlled trials of myeloid growth factors given during induction for AML have been conducted. All of these trials with one exception demonstrated no significant impact on the clinical outcomes of complete response (CR) rate, disease-free, and overall survival. However, the duration of neutropenia was consistently and uniformly reduced by the use of growth factor in all nine of these trials. Because of the favorable impact of the colony-stimulating factors (CSFs) on resource use, antibiotic days, hospital days, etc., it can be more economical and beneficial to use CSFs in AML than to withhold use. The overall dismal outlook for the older AML patient can only be altered by clinical trials with new therapeutic agents. New cellular and molecularly targeted agents are entering clinical trials and bring hope for progress to this area of cancer therapy. PMID:14563517

  15. The Epigenetic Landscape of Acute Myeloid Leukemia

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  16. Genetic abnormalities associated with acute lymphoblastic leukemia.

    Yokota, Takafumi; Kanakura, Yuzuru

    2016-06-01

    Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies. PMID:26991355

  17. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); 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; 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

  18. Distribution of ABO blood group in children with acute leukemias

    Meliha Sakić

    2012-12-01

    Full Text Available Introduction: This study is the fi rst study about the distribution ABO blood types at children with acute leukemia in Federation of Bosnia and Herzegovina. The aim of the study is to point out distribution of blood type groups at children with acute leukemia (ALMethods: The number of children in this study was the following: 145 children with acute leukemia and 27 of children with acute myeloblastic leukemia (AML. All of the children were treated at Hemato- Oncology Unitof Pediatric Clinic in Sarajevo, in the period January 2000 until December 2010. Age of children was between 1 month and 15 years.Results: The results showed that different blood types were registered in 93. 1% of children who got ill and treated from acute leukemia for the mentioned period. At 6. 9 % of children, none of the blood types wereregistered. It was noticed that 40.9 % children who have registered blood type O, 37% blood type A,16% blood type B and 6.5% blood type AB had AL, too. It has been observed that children with following bloodtypes had AML: O, 47.8%, A, 47.7% and AB, 30.4%.Conclusion: Signifi cance ABO types distribution was confi rmed for children with ALL, p<0, 05. The analysis of the distribution of ABO types based on gender showed that signifi cance was confi rmed at females with both ALL and AML (p<0.05.

  19. Fatal lymphoproliferation and acute monocytic leukemia-like disease following infectious mononucleosis in the elderly

    Hehlmann, R.; Walther, B; ZÖLLNER, N.; Wolf, Hans J.; Deinhardt, F; Schmid, M.

    1981-01-01

    Three elderly patients are reported, in whom serologically confirmed recent infectious mononucleosis is followed by fatal lymphoproliferation (case 1), by acute monocytic leukemia (case 2), and by acute probably monocytic leukemia (case 3).

  20. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  1. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  2. General Information about Childhood Acute Lymphoblastic Leukemia

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  3. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  4. Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

    Lin, Tara L.; M. Yair Levy

    2012-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, parti...

  5. Karyotype complexity and prognosis in acute myeloid leukemia

    Stölzel, F.; Mohr, B.; Kramer, M.; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; R. Stuhlmann; Einsele, H; Krause, S W; Serve, H; Hänel, M.; Herbst, R.

    2016-01-01

    A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity...

  6. Vitamin D Protects Acute Lymphoblastic Leukemia Cells from Dexamethasone

    Antony, Reuben; Sheng, Xia; Ehsanipour, Ehsan A.; Ng, Emily; Pramanik, Rocky; Klemm, Lars; Ichihara, Brian; Mittelman, Steven D.

    2012-01-01

    Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have antiproliferative or cytotoxic effects on human pre-B acute lymphoblastic leukemia cells. Contrary to our hypotheses, calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually had a modest effect to impair dexamethasone cytotoxicity and induct...

  7. Temozolomide and cisplatin in relapsed/refractory acute leukemia

    Rasul Muhammad

    2009-05-01

    Full Text Available Abstract Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5. Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25% patients demonstrated a significant reduction in bone marrow blasts.

  8. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Kastner, Philippe; Chan, Susan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene. Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia. Its role in T-cell leukemia, however, has been more controversial. While Ikaros deficiency appears to be very frequent in murine T-cell l...

  9. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    2016-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  10. Cytogenetic studies of Acute Myeloid Leukemia

    Tarek Abd -Alla Atia

    2010-06-01

    Full Text Available Acute myeloid leukemia (AML describes as a group of hematopoietic stem cell disorders characterized by expansion of undifferentiated myeloid progenitors. Acquired chromosomal anomaly particularly reciprocal translocations constitute one of the major events contribute to leukemogenesis. Patient and Methods: 45 untreated, newly diagnosed patients with de novo AML were enrolled in the present study and subjected to cytogenetic analysis. Four ml of heparinized peripheral blood were collected for 72 hours synchronized culture, and then chromosome G- banding analysis was performed using standard methods. The karyotypes were designated according to the International System for Human Cytogenetic Nomenclature (ISCN. The collected data were analyzed statistically. Result: Cytogenetic analysis and karyotype results were obtained in 45 patients with de novo AML. Males constituted 33.3%, and females constituted 66.7% of this group. The patients' age ranged from 17-60 years. Chromosomal anomalies have been detected in 21 out of 45 patients (46.7%. However five different types of chromosome anomalies have been detected; where seven cases (33.3% carrying t(15;17( q22;q21; six cases (28.5% carrying t(8;21(q22;q22; three cases (14.3% had trisomy 8; three cases (14.3% had monosomy 7; and lastly two cases (9.5% carrying inv(3(q21q26. Conclusion: Conventional cytogenetic analysis reliability detects chromosomal abnormalities in AML patients at the time of diagnosis. Chromosomal anomalies detected in Egyptian AML patients, are similar to some extent to those recorded in other areas of the world

  11. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  12. Diagnosis and treatment of acute and chronic leukemia

    The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other neoplastic conditions of the reticuloendothelial system, lymphatic system, spleen, multiple myeloma, macroglobulinemia and other monoclonal gammopathies are excluded, and will be coveted by other Cancergrams now under development. This Cancergram includes abstracts concerning all clinical aspects of the disease, such as diagnosis and staging, supportive care, evaluation, and therapy. Animal models, tissue culture experiments, carcinogenesis and other pre-clinical studies are generally excluded, except for those considered to have direct clinical relevance

  13. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    2015-12-30

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  14. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    ... Learn About Cancer » Leukemia - Acute Lymphocytic (ALL) in Adults » Detailed Guide » What’s new in acute lymphocytic leukemia ... What`s New in Leukemia - Acute Lymphocytic (ALL) in Adults Research? TOPICS Document Topics GO » SEE A LIST » ...

  15. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia

    Levine, Ross L; Loriaux, Marc; Huntly, Brian J.P.; Loh, Mignon L.; Beran, Miroslav; Stoffregen, Eric; Berger, Roland; Clark, Jennifer J; Willis, Stephanie G; Kim T. Nguyen; Flores, Nikki J.; Estey, Elihu; Gattermann, Norbert; Armstrong, Scott; Look, A. Thomas

    2005-01-01

    Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (A...

  16. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas;

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  17. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  18. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2016-07-08

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  19. Acute Myeloid Leukemia (AML) (For Parents)

    ... fluid (CSF, the fluid surrounding the brain and spinal cord) for examination in a lab. Flow cytometry tests. Using markers on leukemia cells collected from the blood, bone marrow, and/or CSF, doctors can determine the type ...

  20. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40 sup tax protein in the human T-cell line, Jurkat

    Nagata, Kinya; Ohtani, Kiyoshi; Nakamura, Masataka; Sugamura, Kazuo (Tohoku Univ. School of Medicine, Sendai (Japan))

    1989-08-01

    The authors examined the ability of the trans-acting factor p40{sup tax} of human T-cell leukemia virus type I (HTLV-I), which is thought to be a crucial molecule in T-cell transformation by HTLV-I, to activate expression of a set of endogenous cellular genes related to T-cell proliferation. For this purpose, they established a subclone (JPX-9) of Jurkat cells that was stably transfected with an expression plasmid containing the p40{sup tax} gene, whose expression is definitively dependent on heavy-metal ions. Expression of the interleukin-2 receptor {alpha} chain in JPX-9 cells was induced in response to the induction of p40{sup tax} expression, as has been demonstrated by others in transient transfection experiments with Jurkat cells. In addition, they found that significant enhancement of expression of the nuclear proto-oncogene c-fos was closely associated with expression of p40{sup tax}. Continuous enhancement in the level of c-fos mRNA was observed in the presence of p40{sup tax}. These results suggest that (i) in addition to the interleukin-2-interleukin-2 receptor system, cellular genes such as c-fos, which regulate normal T-cell growth, are also activated directly or indirectly by p40{sup tax} and (ii) p40{sup tax}-induced modulation of gene expression plays a crucial role in T-cell transformation by HTLV-I.

  1. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

    Bekker-Méndez Vilma

    2011-08-01

    Full Text Available Abstract Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR, and the standardized average annual incidence rates (SAAIR per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level. Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3; acute lymphoblastic leukemia (ALL was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million, followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million, and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million. The 1-4 years age group had the highest SAAIR for ALL (77.7 per million. For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million. The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8% were

  2. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound.

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4'-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID:26360247

  3. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound.

    Maia Cabrera

    Full Text Available Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC compounds, we have previously identified 4,4'-dimethoxybenzophenone thiosemicarbazone (T44Bf as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat. Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies.

  4. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline

    2015-01-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance ...

  5. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Stephen E. Langabeer

    2016-01-01

    Full Text Available The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

  6. Down-regulation of 11β-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis.

    Yi Tao

    Full Text Available 11β-Hydroxysteroid dehydrogenases type 2 (11β-HSD2, a key regulator for pre-receptor metabolism of glucocorticoids (GCs by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

  7. Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

    2015-11-16

    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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

  8. Pharmacokineties of vincristine monotherapy in childhood acute lymphoblastic leukemia

    Groninger, E; Meeuwsen-de Boer, T; Koopmans, P; UGes, D; Sluiter, W; Veerman, A; Kamps, W

    2002-01-01

    We studied vincristine pharmacokinetics in 70 children newly diagnosed with acute lymphoblastic leukemia, after a single dose of vincristine as monotherapy. Vincristine plasma concentrations were measured by HPLC analysis. A two-compartment, first-order pharmacokinetic model was fitted to the data b

  9. Vascular endothelial growth factor signaling in acute myeloid leukemia

    Kampen, Kim R.; ter Elst, Arja; de Bont, Eveline S. J. M.

    2013-01-01

    This review is designed to provide an overview of the current literature concerning vascular endothelial growth factor signaling (VEGF) in acute myeloid leukemia (AML). Aberrant VEGF signaling operates in the bone marrow of AML patients and is related to a poor prognosis. The altered signaling pathw

  10. Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

    ... myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations. Ann N Y Acad Sci. 2014 Mar;1310:111-8. doi: ... 17, 2016 The resources on this site should not be used as a substitute for professional medical care or advice. Users with questions about a ...

  11. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  12. Radiotherapy of the central nervous system in acute leukemia

    The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.20 references

  13. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.;

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  14. Molecular mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia

    W.J.E. Tissing (Wim)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) is the most common form of cancer in children, with 110 – 120 newly diagnosed children in the Netherlands each year. ALL is a haematological malignancy of lymphoid precursor cells and can be divided into two sub-groups: B-cell precursor ALL and T-cell p

  15. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe;

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...

  16. Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11) leukemia with lineage switch and extreme leukocytosis

    Čolović Nataša; Bogdanović Andrija; Virijević Marijana; Vidović Ana; Tomin Dragica

    2015-01-01

    Introduction. In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI) during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. Case Outline....

  17. The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells

    Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3β inhibitor, on several ALL cell lines. ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points. PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 μM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase. PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL

  18. Down-regulation of β-catenin Nuclear Localization by Aspirin Correlates with Growth Inhibition of Jurkat Cell Line

    2006-01-01

    In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA,and cell cycle of Jurkat cell line (Human T-acute lymphoblastic leukemia). Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of β-catenin, and at 5 mmol/L of aspirin,the nuclear localization of β-catenin was undetectable. QRT-PCR showed that the target gene cyclinD1 mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through β-catenin-independent mechanisms. The effects of aspirin include down-regulation of β-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.

  19. Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.

    Horie, Yukiko; Nemoto, Hideyuki; Itoh, Mari; Kosaka, Hiroaki; Morita, Kyoji

    2016-04-01

    Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner. The reduction of the cell viability was accompanied by the DNA fragmentation, and partially restored by treatment with pan-caspase inhibitor. Further studies showed that FBRA extract induced the cleavage of caspase-8, -9, and -3, and decreased Bcl-2 protein expression. Moreover, the expression of tBid, DR5, and Fas proteins was enhanced by FBRA extract, and the pretreatment with caspase-8 inhibitor, but not caspase-9 inhibitor, restored the reduction of the cell viability induced by FBRA extract. These findings suggested that FBRA extract could induce the apoptotic death of human acute lymphoblastic leukemia cells probably through mainly the death receptor-mediated pathway and supplementarily through the tBid-mediated mitochondrial pathway, proposing the possibility that FBRA was a potential functional food beneficial to patients with hematological cancer. PMID:26769704

  20. Leukemias

    Riccardo Masetti

    2011-01-01

    Full Text Available Acute leukemia is the most common type of childhood and adolescence cancer, characterized by clonal proliferation of variably differentiated myeloid or lymphoid precursors. Recent insights into the molecular pathogenesis of leukemia have shown that epigenetic modifications, such as deacetylation of histones and DNA methylation, play crucial roles in leukemogenesis, by transcriptional silencing of critical genes. Histone deacetylases (HDACs are potential targets in the treatment of leukaemia, and, as a consequence, inhibitors of HDACs (HDIs are being studied for therapeutic purposes. HDIs promote or enhance several different anticancer mechanisms, such as apoptosis, cell cycle arrest, and cellular differentiation and, therefore, are in evidence as promising treatment for children and adolescents with acute leukemia, in monotherapy or in association with other anticancer drugs. Here we review the main preclinical and clinical studies regarding the use of HDIs in treating childhood and adolescence leukemia.

  1. A possible role for WNT5A hypermethylation in Pediatric Acute Lymphoblastic Leukemia

    Özden Hatırnaz Ng

    2015-06-01

    Full Text Available INTRODUCTION: WNT5A is one of the most studied noncanonical WNT ligands and is shown to be deregulated in different tumor types. Our aim was to clarify whether hypermethylation might be the cause of low WNT5A mRNA levels and whether we could restore this downregulation by reversing the event. METHODS: The expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia (ALL patient group (n=86 by quantitative real-time PCR. The methylation status was detected by methylation-specific PCR (MSPCR and bisulphate sequencing. In order to determine whether methylation has a direct effect on WNT5A expression, disease-representative cell lines were treated by 5’-aza-20-deoxycytidine. RESULTS: Here we designed a validation experiment of the WNT5A gene, which was previously examined and found to be differentially expressed by microarray study in 31 T-cell ALL patients. The expression levels were confirmed by quantitative real-time PCR and the expression levels were significantly lower in T-cell ALL patients than in control thymic subsets (p=0.007. MSPCR revealed that 86% of the patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell lines were treated with 5’-aza-20-deoxycytidine and WNT5A mRNA expression was restored after treatment. DISCUSSION AND CONCLUSION: According to our results, WNT5A hypermethylation does occur in ALL patients and it has a direct effect on mRNA expression. Our findings show that epigenetic changes of WNT signaling can play a role in ALL pathogenesis and reversing methylation might be useful as a possible treatment of leukemia.

  2. BCL11A expression in acute phase chronic myeloid leukemia.

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  3. Oral health of children with acute lymphoblastic leukemia: A review

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  4. Radiation treatment of testicular relapse in acute lymphoblastic leukemia

    Ten patients with testicular relapse among 128 cases of acute lymphoblastic leukemia are reported. At the time of the initial diagnosis of leukemia all patients with later testicular relapse showed one or more risk factors as predictive for leukemic infiltration of the testicles. All patients except one, who underwent orchiectomy and died 11 weeks after surgical intervention, received radiation therapy with doses ranging from 12 to 20 Gy and chemotherapy. The local control was excellent. Average survival time from testicular relapse to death was 68 weeks in 8 of 9 patients treated by irradiation and chemotherapy. One patient is still alive without signs of disease after 6 years. (orig.)

  5. 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

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; 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

  6. Acute leukemia of childhood: A single institution's experience

    Slavković Bojana

    2005-01-01

    Full Text Available The aim of this study was to investigate distribution of immunophenotypic and cytogenetic features of childhood acute leukemia (AL in the cohort of 239 newly diagnosed patients registered at the leading pediatric oncohematology center in the country during a six-year period (1996-2002. With approximately 60-70% of all childhood AL cases in Serbia and Montenegro being diagnosed and treated in this institution the used data represent a valid research sample to draw conclusions for entire country. On the basis of five phenotypic markers, the distribution of immunological subtypes was as follows: 169 (70.7% expressed B-cell marker CD19 (137 were CD10 positive and 32 CD10 negative, 37 (15.5% belonged to T-lineage acute lymphoblastic leukemia (T-ALL (cyCD3 positive, and 33 (13.8% were acute myeloblastic leukemia (AML (CD13 positive and/or CD33 positive in the absence of lymphoid-associated antigens. The ratio of males and females was 1.5:1. Most of the cases were between the ages of 2 and 4, and were predominantly B-lineage acute lymphoblastic leukemia (B-ALL cases. Another peak of age distribution was observed at the age of 7. The frequency of T-ALL (18% of ALL was similar to that reported for Mediterranean countries: France (19.4%, Greece (28.1%, Southern Italy (28.3%, and Bulgaria (28.0%. Cytogenetic analyses were performed in 193 patients: 164 ALL and 29 AML. Normal karyotype was found in 57% of ALL and in 55% of AML patients, while cytogenetic abnormalities including structural, numerical, and complex chromosomal rearrangements were found in 43% of ALL and in 45% of AML patients. Our results represent a contribution to epidemiological aspects of childhood leukemia studies.

  7. Acute Hepatitis A Induction of Precursor B-Cell Acute Lymphoblastic Leukemia: A Causal Relationship?

    Senadhi, V.; Emuron, D.; R. Gupta

    2010-01-01

    Background Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. Case Report We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with mala...

  8. The acute lymphoblastic leukemia of Down Syndrome - Genetics and pathogenesis.

    Izraeli, Shai

    2016-03-01

    Children with Down Syndrome (DS) are at markedly increased risk for acute lymphoblastic leukemia (ALL). The ALL is of B cell precursor (BCP) phenotype. T-ALL is only rarely diagnosed as well as infant leukemia. Gene expression profiling and cytogenetics suggest that DS-ALL is an heterogeneous disease. More than half of the leukemias are characterized by aberrant expression of the thymic stromal lymphopoietin (TSLP) receptor CRLF2 caused by genomic rearrangements. These rearrangements are often associated with somatic activating mutations in the receptors or in the downstream components of the JAK-STAT pathway. The activation of JAK-STAT pathway suggests that targeted therapy with JAK or downstream inhibitors may be effective for children with DS-ALL. The basis of the increased risk of BCP-ALL and in particular of the CRLF2 aberrations is presently unknown. Neither is it known which genes on the trisomic chromosome 21 are involved. PMID:26631987

  9. Side effects of treatment in childhood acute leukemia, 2

    We evaluated delayed neurotoxicities in treatment of childhood acute leukemia. Of 28 patients treated over 2 years who were examined on computed tomography of brain scans, 7 patients had abnormal findings. These abnormalities included two cases of leukoencephalopathy, three cases of intracranial calcifications, and two of ventricular dilatation. These patients were under 6 years old at the onset of disease, especially under 3 years old. Also, delayed neurotoxicities developed after relapse of leukemia, especially CNS relapse. It was considered that these were caused by cranial irradiation, intravenous methotrexate injection, intrathecal methotrexate, and sometimes high-dose Ara-C therapy, etc. Most of the cases of leukoencephalopathy were associated with treatment of intermediate-dose or high-dose methotrexate after relapse. These abnormalities must be carefully considered in the treatment of younger children with leukemia and patients with relapse. (author)

  10. Spectrum of acute and chronic leukemia at a tertiary care hospital, Haryana, India

    Gajender Singh; Padam Parmar; Sant Prakash Kataria; Sunita Singh; Rajeev Sen

    2016-01-01

    Background: Leukemias are primary neoplasms arising from the malignant proliferations of blood cells or their precursors. Leukemias are classified into acute/chronic myeloid and lymphoid subtype. Typing of leukemia is essential for effective therapy because prognosis and survival rate are different for each type and sub-type. Methods: A total of 356 patients diagnosed to have acute/chronic leukemia were included in our study. Only newly diagnosed cases were included in this study and patie...

  11. Prevalence of transient hyperglycemia and diabetes mellitus in pediatric patients with acute leukemia

    Banihashem, A; Ghasemi, A.; N. Ghaemi; Moazzen, N; Amirabadi, A

    2014-01-01

    Background The most common malignancy of children is Leukemia, accounting approximately one third of cancer diagnosis. Available data demonstrate improvement in survival of pediatric leukemia, so evaluation of side effects of treatment is very important. This study investigates hyperglycemia and diabetes mellitus prevalence in pediatric patients with acute leukemia. Materials and Methods This study was performed in children with acute leukemia. At the first admission, demographic data was col...

  12. Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

    Kampa-Schittenhelm, Kerstin Maria; Salitzky, Olaf; Akmut, Figen; Illing, Barbara; Kanz, Lothar; Salih, Helmut Rainer; Schittenhelm, Marcus Matthias

    2016-01-01

    Background It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. Methods To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 ...

  13. Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

    Sherborne, Amy L.; Hemminki, Kari; Kumar, Rajiv; Bartram, Claus R.; Stanulla, Martin; Schrappe, Martin; Petridou, Eleni; Semsei, Ágnes F.; Szalai, Csaba; Sinnett, Daniel; Krajinovic, Maja; Healy, Jasmine; Lanciotti, Marina; Dufour, Carlo; Indaco, Stefania; El-Ghouroury, Eman A; Sawangpanich, Ruchchadol; Hongeng, Suradej; Pakakasama, Samart; Gonzalez-Neira, Anna; Ugarte, Evelia L.; Leal, Valeria P.; Espinoza, Juan P.M.; Kamel, Azza M.; Ebid, Gamal T.A.; Radwan, Eman R.; Yalin, Serap; Yalin, Erdinc; Berkoz, Mehmet; Simpson, Jill; Roman, Eve; Lightfoot, Tracy; Hosking, Fay J.; Vijayakrishnan, Jayaram; Greaves, Mel; Houlston, Richard S.

    2011-01-01

    Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be

  14. FLT3 mutations in canine acute lymphocytic leukemia

    FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations. We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting. The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations. These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias

  15. A case of acute lymphoblastic leukemia with an intracerebellar mass

    A 3-year-old boy, who had a complaint of hemorrhagic diathesis, was diagnosed as having acute lymphoblastic leukemia. Remission was induced by a combination of vincristine and prednisolone. Prophylactic intrathecal methotrexate and cranial irradiation were administered. Two years later, he was hospitalized for CNS leukemia and treated with multiple doses of intrathecal methotrexate. At the time, the results of CT scanning were normal. Six months later, though, he developed vomiting and lethargy. CT scanning showed a mass of an increased density in the right cerebellar hemisphere that displaced the fourth ventricle to the left and resulted in an obstructive hydrocephalus. Decompression was done by means of Ommaya reservoir setting. Soon his consciousness returned to normal, and CT scanning revealed no abnormal mass three weeks later. A month later, though, the CNS leukemia returned. He developed vomiting and a headache, and CT scanning showed a high-density mass in the right cerebellar hemisphere. The mass was diagnosed as hematoma. He died one month later. In this case, the previous mass showed evidence of a relatively uniform contrast enhancement, which is consistent with the intracerebral leukemic mass reported by Wendling. In Japan, this is the first report of an intracerebellar mass of acute lymphoblastic leukemia as perceived by CT scanning. (author)

  16. Acute parotitis during induction therapy including L-asparaginase in acute lymphoblastic leukemia.

    Sica, S; Pagano, L; Salutari, P; Di Mario, A; Rutella, S; Leone, G

    1994-02-01

    In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase. PMID:8148421

  17. Acute megakaryoblastic leukemia with increased hematogones in children.

    Anton-Harisi, Marieta; Douna, Varvara; Baka, Margarita; Servitzoglou, Marina; Kosmidis, Helen V; Georgouli, Helen; Anastasiou, Theodora

    2012-11-01

    We describe 2 patients, a 4-month-old male and a 17-month-old female, with de novo acute megakaryoblastic leukemia with increased number of hematogones at diagnosis. Both children were admitted in the hospital with thrombocytopenia. The bone marrow smears in the first child revealed the presence of 60% cells with morphologic features consistent with acute megakaryoblastic leukemia. In the other, the initial bone marrow aspirate was dry tap but on the following aspirate 10% cells with lymphoblastic morphology could be seen. The bone marrow flow cytometry showed the presence of hematogones-38% in the first case and 20% in the second-with absence of blasts. Repeated bone marrow aspirates, trephines, and immunophenotypic as well as molecular studies, confirmed the diagnosis of M7. Both children were treated according to the Berlin-Frankfurt-Munster 2004 protocol. PMID:22983420

  18. Acute lymphoblastic leukemia in a child with fanconi's anaemia

    Fanconi anaemia (FA) is an autosomal recessive inherited disorder with progressive bone marrow failure, associated congenital malformation and solid and haematological malignancies. Acute myeloid leukemia is the commonest haematological malignancy followed by myelodysplastic syndrome in children with FA. FA transformed into acute lymphoblastic leukemia (ALL) is a rare phenomenon and one of the rarest haematological malignancies associated with this disorder. We are reporting a 13 years old girl with FA and positive chromosomal breakage. She required regular blood product transfusion. She was planned for haematopoietic stem cell transplantation (HSCT) but the sibling-matched donor was found to have chromosomal breaks as well. Later on, her peripheral smear showed blast cell. Bone marrow showed pre-B ALL. She was started on chemotherapy but died shortly due to complications of the treatment. For this rare condition conservative management is indeed essential, however, safe and appropriate chemotherapy regimen is needed. (author)

  19. New decision support tool for acute lymphoblastic leukemia classification

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  20. Genetics Home Reference: acute promyelocytic leukemia

    ... Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010 Nov;10( ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  1. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Shiek Aejaz Aziz; Susheel Kumar Sharma; Iram Sabah; M Aleem Jan

    2015-01-01

    Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL) patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 p...

  2. Allogeneic stem cell transplantation in acute myeloid leukemia

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  3. Amifostine Treatment of a Patient with Refractory Acute Myeloid Leukemia

    Tekgündüz, Emre; ERİKÇİ, ALEV AKYOL; Ahmet ÖZTÜRK

    2009-01-01

    The prognosis for the majority of acute myeloid leukemia (AML) patients without a donor is dismal whether conventional salvage chemotherapy regimens or investigational strategies are used, and most of these patients will eventually die of their disease. There is no standard chemotherapy regimen that provides durable complete remission in patients with refractory AML. Beneficial effects of amifostine, either alone or in combination with conventional chemotherapy, was demonstrated in patients w...

  4. Minimal Residual Disease Assessment in Childhood Acute Lymphoblastic Leukemia

    Thörn, Ingrid

    2009-01-01

    Traditionally, response to treatment in hematological malignancies is evaluated by light microscopy of bone marrow (BM) smears, but due to more effective therapies more sensitive methods are needed. Today, detection of minimal residual disease (MRD) using immunological and molecular techniques can be 100 times more sensitive than morphology. The main aim of this thesis was to compare and evaluate three currently available MRD methods in childhood acute lymphoblastic leukemia (ALL): (i) real-t...

  5. Estimation of physical development of children at acute lymphoblastic leukemia

    The problem of the work is data of 124 children with acute lymphoblastic leukemia and Hodgkin's disease after combination treatment.The objective of the work is to detect physical stature of children after cancer therapy in children and comparison of their antropometrical data before and after therapy.The possibility of detection of combination therapy's influence on physical stature of children in remission was shown. (authors)

  6. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  7. Acute lymphoblastic leukemia: Are Egyptian children adherent to maintenance therapy?

    Elhamy Rifky Abdel Khalek; Laila M Sherif; Naglaa Mohamed Kamal; Gharib, Amal F.; H M Shawky

    2015-01-01

    Background, Aims, Settings and Design: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL). A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP) maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. Materials and Methods: The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening....

  8. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia

    Emadi, Ashkan; Karp, Judith E.

    2012-01-01

    Acute myelogenous leukemia (AML) is an extremely heterogeneous neoplasm with several clinical, pathological, genetic and molecular subtypes. Combinations of various doses and schedules of cytarabine and different anthracyclines have been the mainstay of treatment for all forms of AMLs in adult patients. Although this combination, with the addition of an occasional third agent, remains effective for treatment of some young-adult patients with de novo AML, the prognosis of AML secondary to myel...

  9. A robust xenotransplantation model for acute myeloid leukemia

    Sanchez, PV; Perry, RL; Sarry, JE; Perl, AE; Murphy, K.; Swider, CR; Bagg, A; Choi, JK; Biegel, JA; Danet-Desnoyers, G; Carroll, M.

    2009-01-01

    Xenotransplantation of human acute myeloid leukemia (AML) in immunocompromised animals has been critical for defining leukemic stem cells. However, existing immunodeficient strains of mice have short life spans and low levels of AML cell engraftment, hindering long-term evaluation of primary human AML biology. A recent study suggested that NOD/LtSz-scid IL2Rγc null (NSG) mice have enhanced AML cell engraftment, but this relied on technically challenging neonatal injections. Here, we performed...

  10. Functional Integration of Acute Myeloid Leukemia into the Vascular Niche

    Cogle, Christopher R.; Goldman, Devorah C.; Madlambayan, Gerard J; Leon, Ronald P.; Masri, Azzah Al; Clark, Hilary A.; Asbaghi, Steven A.; Tyner, Jeffrey W.; Dunlap, Jennifer; Fan, Guang; Kovacsovics, Tibor; Liu, Qiuying; Meacham, Amy; Hamlin, Kimberly L.; Hromas, Robert A.

    2014-01-01

    Vascular endothelial cells are a critical component of the hematopoietic microenvironment that regulates blood cell production. Recent studies suggest the existence of functional cross-talk between hematologic malignancies and vascular endothelium. Here, we show that human acute myeloid leukemia (AML) localizes to the vasculature in both patients and in a xenograft model. A significant number of vascular tissue-associated AML cells (V-AML) integrate into vasculature in vivo and can fuse with ...

  11. Recent advances in the treatment of acute myeloid leukemia

    Abdel-Wahab, Omar; Levine, Ross L.

    2010-01-01

    Acute myeloid leukemia (AML) is a disorder with significant molecular and clinical heterogeneity. Although there have been clear advances in the identification of somatic genetic and epigenetic alterations present in the malignant cells of patients with AML, translating this knowledge into an integrated view with an impact on the clinical treatment of AML has been slower to evolve. Recent clinical advances in the treatment of AML include studies demonstrating the benefit of dose-intense dauno...

  12. Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues

    1981-01-01

    The common acute lymphoblastic leukemia antigen (CALLA), as defined by J-5 murine monoclonal antibodies, was detected on renal tubular and glomerular cells from fetal and adult donors by an indirect immunoperoxidase technique. CALLA could also be detected on epithelial cells of the fetal small intestine and on myoepithelial cells of adult breast but not on myoepithelial cells of the salivary gland. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated 125I-l...

  13. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Langabeer, Stephen E.; Karl Haslam; David O’Brien; Johanna Kelly; Claire Andrews; Ciara Ryan; Richard Flavin; Hayden, Patrick J.; Bacon, Christopher L.

    2016-01-01

    The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to...

  14. New Fusion Transcripts Identified in Normal Karyotype Acute Myeloid Leukemia

    Hongxiu Wen; Yongjin Li; Malek, Sami N.; Kim, Yeong C.; Jia Xu; Peixian Chen; Fengxia Xiao; Xin Huang; Xianzheng Zhou; Zhenyu Xuan; Shiva Mankala; Guihua Hou; Rowley, Janet D.; Zhang, Michael Q; San Ming Wang

    2012-01-01

    Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analy...

  15. Chromosome aberrations and environmental exposures in acute leukemia

    Lindquist, Ragnhild Rosengren

    2009-01-01

    The aims of this thesis are to evaluate the role of environmental exposures, especially professional exposure to organic solvents and petroleum products in the etiology of acute leukemia and to investigate if there is a correlation between the exposure to a specific leukemogen factor and a clonal chromosome aberration of the leukemic cells. Papers I and II present results of a case-control study of environmental exposures, in all occupations during life-time, medical treatm...

  16. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  17. [Expression of HoxA10 in acute leukemia and its significance].

    Huang, Ying; Li, Wei-Jia; Wei, Cai-Xia; Zhou, Zhi; Nie, Bo

    2005-12-01

    To investigate the expression of HoxA(10) mRNA in acute leukemia patients and its significance, HoxA(10) level was detected by reverse transcription polymerase chain reaction (RT-PCR) in 50 patients with acute leukemias, 7 healthy volunteers and 3 patients with ITP (idiopathic thrombocytopenic purpura). The regularity of the expression of HoxA(10) gene in acute leukemia and the relationship between HoxA(10) level and the prognosis of leukemia was explored. The results showed that HoxA(10) was expressed in all types of acute myelogenous leukemia; HoxA(10) message was also observed in acute lymphoblastic leukemia patients and part of control groups. 3 normal donors were found not to express HoxA(10). The level of HoxA(10) mRNA of acute myelogenous leukemia patients was significantly higher than that of acute lymphoblastic leukemia patients and controls (P acute promyelocytic leukemia. The number of blast and promyeloid cells in the bone marrow was positive related with the level of HoxA (r = 0.635, P acute myelogenous leukemia. It is concluded that HoxA(10) is a major transcription factor regulating hematopoiesis and a mark to differentiate lymphoid leukemia and myelogenous leukemia, but not a specific gene of cancer. The level of HoxA(10) is related with load of leukemic cells and curative effect, and can affect occurrence and development of leukemia in combination with many cytokines, HoxA(10) may facilitate the leukemia progression with another cofactors. PMID:16403259

  18. Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

    Lee, Jae Hee; Yoon, Hoi Soo; Song, Joon Sup; Choi, Eun Seok; Moon, Hyung Nam; Seo, Jong Jin; Im, Ho Joon

    2009-01-01

    We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients...

  19. Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia

    Sushma Belurkar; Himabindu Mantravadi; Chethan Manohar; Annamma Kurien

    2013-01-01

    Introduction: The classification of acute leukemias has revolutionized over the years. Immunophenotyping of acute leukemia has gained popularity because of its influence on treatment and prognosis of the disease. The various antigens expressed by the leukemic cells can be assessed by flowcytometry (FCA) and can be used in rendering specific treatment and predicting the outcome of the different types of acute leukemia. Aims: The main aim of this study was to compare the morphologic and cyt...

  20. Pancytopenic Prodrome (pre-ALL) of Acute Lymphoblastic Leukemia in Adults: Possible Pathogenesis

    Sohn, Sang Kyun; Suh, Jang Soo; Lee, Jaetae; Lee, Kyu Bo

    1998-01-01

    We report two cases of adult acute lymphoblastic leukemia presenting with preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone marrow aspirates. The initial diagnosis of each case was suspicious aplastic anemia and hypoplastic anemia. Both cases progressed to overt acute lymphoblastic leukemia within 1 year. We suggest that initial pancytopenic phase (pre-ALL) may precede the diagnosis of acute lymphoblastic leukemia in adults and differential diagnosis from myelodyspl...

  1. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

  2. Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia.

    Santos, G W

    1988-01-01

    Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed. PMID:3052840

  3. Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

    Takahashi, Isao; Sekito,Noriko; Takeuchi, Makoto; Osada, Ken; Matsuzaki,Toshiro; Fukuda, Shunichi; Lai,Minyu; Uchida, Kozaburo; Kimura,Ikuro; Miyamoto,Kanji; Kitajima,Koichi; Sanada, Hiroshi

    1988-01-01

    The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocyt...

  4. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup.

    Huguet, Françoise; Leguay, Thibaut; Raffoux, Emmanuel; Rousselot, Philippe; Vey, Norbert; Pigneux, Arnaud; Ifrah, Norbert; Dombret, Hervé

    2015-04-01

    Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m(2)/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. PMID:24996442

  5. Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

    2013-08-06

    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); Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  6. Acute leukemia case presented with hypercalcemia

    Mehmet Selçuk Bektaş

    2015-10-01

    Full Text Available An 8-year-old girl patient referred to our emergency clinic with articular pain, stomachache and fever complaints. Past history revealed that she was suffering from pain in both knees and ankle joints for 8 days. The joint temperature increased and swelling did not accompany articular pain. Family history was unremarkable. In the physical examination, there was sensitivity in the knees, elbows and ankles during movement. The patient had normal complete blood cell count, and no blast or atypical cells were observed in peripheral smear. Serum electrolytes, liver and kidney function tests were normal except for hypercalcemia. The 25 (OH vitamin D and 1-25 (OH2 vitamin D levels were within normal range. In bone marrow aspiration, infiltration of cells with lymphoblastic and homogenous cellular features was observed. With positivity of cCD79, CD19, CD45, the case was considered as preB cell leukemia. Body bone scintigraphy performed for bone metastasis was normal. After the chemotherapy, hydration and furosemid treatment, the calcium level returned to normal. This case emphasized on the fact that, children with hypercalcemia should undergo a detailed examination for malignancies even though no blast or atypical lymphocyte are observed in their peripheral blood smear before steroid treatment is applied and if necessary, bone marrow aspiration should be taken into account.

  7. Bony Lesions in Pediatric Acute Leukemia: Pictorial Essay

    Makhtoom Shahnazi

    2012-03-01

    Full Text Available Acute leukemia is the most common malignancy in childhood, which mainly involves children less than 15 years of age. The growing skeleton is the main site of involvement in children. Leukemic cells proliferate within the massive red bone marrow in children. So besides the pallor, petechia, purpura and ecchymosis in the skin and mucosal surfaces, bone pain and other bony lesions are other manifestations of leukemia.On the other hand, bony lesions are more prevalent in children than adults with no poor prognosis in comparison to patients without bone lesions. These bony lesions may precede other laboratory tests so familiarity with these presentations is very important for earlier diagnosis.In this pictorial essay, we tried to gather the most common bony lesions that may be seen in acute leukemia in different cases admitted to our hospital with general malaise and localized tenderness and discomfort leading us to perform plain X-ray for further evaluation. Finding these bony lesions helps clinicians to reach the diagnosis quickly. These findings include metaphyseal lucent band and erosion, periosteal reaction, small lucent bone lesion and permeative appearance, reduced bone density and collapsed vertebra.

  8. Imitation of Mb. perthes through acute lymphoblastic leukemia

    A two year old boy was seen in the orthopedic clinics because of typical symptoms of Legg-Perthes disease, a scintigraphy with Technetium sup(99m) showed a distinct deficiency of nuclear activity in the femoral head which is characteristic of the early stage of Legg-Perthes disease. A routine blood count lead to the diagnosis of acute lymphoblastic leukemia. The boy was treated according to the Austrian cooperative leukemia protocol and complete remission was achieved. No orthopedic treatment of the femur head necrosis was done, after eight weeks of treatment with multiagent chemotherapy the boy started to walk again and subsequently became free of all symptoms of Legg-Perthes disease. A scintigraphy done eight weeks after the initial scintigraphy showed that the deficiency of radionuclear activity of the femoral head was nearly vanished. This case illustrates the variability of bone involvement in acute lymphoblastic leukemia, which often is the most prominent symptom at an early stage of the disease. (Author)

  9. Aggressive chemotherapy for acute leukemia relapsed after transplantation.

    Sica, S; Salutari, P; Di Mario, A; D'Onofrio, G; Etuk, B; Leone, G

    1994-09-01

    Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival. PMID:7858490

  10. Haploidentical Transplantation in Children with Acute Leukemia: The Unresolved Issues

    Sarita Rani Jaiswal

    2016-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT remains a curative option for children with high risk and advanced acute leukemia. Yet availability of matched family donor limits its use and although matched unrelated donor or mismatched umbilical cord blood (UCB are viable options, they fail to meet the global need. Haploidentical family donor is almost universally available and is emerging as the alternate donor of choice in adult patients. However, the same is not true in the case of children. The studies of haploidentical HSCT in children are largely limited to T cell depleted grafts with not so encouraging results in advanced leukemia. At the same time, emerging data from UCBT are challenging the existing paradigm of less stringent HLA match requirements as perceived in the past. The use of posttransplantation cyclophosphamide (PTCY has yielded encouraging results in adults, but data in children is sorely lacking. Our experience of using PTCY based haploidentical HSCT in children shows inadequacy of this approach in younger children compared to excellent outcome in older children. In this context, we discuss the current status of haploidentical HSCT in children with acute leukemia in a global perspective and dwell on its future prospects.

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

    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)

  12. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    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.)

  13. B lineage acute lymphoblastic leukemia transformation in a child with juvenile myelomonocytic leukemia, type 1 neurofibromatosis and monosomy of chromosome 7. Possible implications in the leukemogenesis

    Scrideli, Carlos Alberto; Baruffi, Marcelo Razera; Rogatto, Silvia Regina;

    2003-01-01

    This report describes the case of an 8-month-old infant with a diagnosis of juvenile myelomonocytic leukemia (JMML) and type 1 neurofibromatosis that presented progression to B lineage acute lymphoid leukemia (ALL). The same rearrangement of gene T-cell receptor gamma (TCR gamma) was detected upon...... may be the cause of JMML and acute leukemia....

  14. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Jian-Hua Yu; Jing-Tao Dong; Yong-Qian Jia; Neng-Gang Jiang; Ting-Ting Zeng; Hong Xu; Xian-Ming Mo

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease.We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development,including IL-7Rα (CD127),cytoplasmic CD79a (cCD79a),CD19,VpreB (CD179a),and slgM,which are successive and essential for progression of B cells along their developmental pathway.Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous,with the leukemic cell population differing from case to case.Through the comprehensive analysis of immunophenotypic patterns,the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis,therapeutic monitoring,and individualized therapies for common ALL.

  15. Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo, Induces Apoptosis in a T-Cell Leukemia Cell Line, Jurkat E6-1

    Courtney Bennett

    2013-08-01

    Full Text Available Representatives of Subclass Elasmobranchii are cartilaginous fish whose members include sharks, skates, and rays. Because of their unique phylogenetic position of being the most primitive group of vertebrates to possess all the components necessary for an adaptive immune system, the immune regulatory compounds they possess may represent the earliest evolutionary forms of novel compounds with the potential for innovative therapeutic applications. Conditioned medium, generated from short term culture of cells from the epigonal organ of bonnethead sharks (Sphyrna tiburo, has been shown to have potent reproducible cytotoxic activity against a variety of human tumor cell lines in vitro. Existing data suggest that epigonal conditioned medium (ECM exerts this cytotoxic activity through induction of apoptosis in target cells. This manuscript describes apoptosis induction in a representative tumor cell line, Jurkat E6-1, in response to treatment with ECM at concentrations of 1 and 2 mg/mL. Data indicate that ECM exposure initiates the mitochondrial pathway of apoptosis through activation of caspase enzymes. Future purification of ECM components may result in the isolation of an immune-regulatory compound with potential therapeutic benefit for treatment of human cancer.

  16. Expression of Heparanase Gene in Egyptian Acute Leukemia Patients

    Samir Attia Mohamed Zaahkouk. a, Seham Omar Mohamed Ibrahim b; Amira Ahmed Hammam b ; Hesham Fathy Hedifa

    2014-04-01

    Full Text Available Background: Heparanase is an endoglycosidase that degrades heparin sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Expression of the heparanase gene is associated with the invasive, angiogenic, and metastatic potential of diverse malignant tumors and cell lines. Aim of the study: to investigate possible relation/correlation between Heparanase gene expression and quantitation in pediatric Acute leukemia patients and clinicopathologic variables as well as patients outcome in an attempt to determine it′s prognostic value and the possibility of using it as a new target for treatment. Patients and methods: Forty pediatric acute leukemia patients (20 acute myeloid leukemia (AML&20 acute lymphoblastic leukemia(ALL as well as 11 normal volunteers were analyzed for the expression and level of Heparanase gene using real time quantitative reverse transcriptase polymerase chain reaction (RTQ-PCR to investigate a possible relation, association, or correlation with the clinical and laboratory features of patients at diagnosis, and patient outcome after treatment and follow up. Results: Comparing the 3 groups as regards the Heparanase gene level there was high statistical significant difference (p<0.001 being maximum in AML and minimum in controls, with mean Relative quantitation (RQ level 2336.2± 10405.2 in AML ,median 8.0 and range (3.1-46543.0 , while mean RQ in ALL was 1.7±1.0 ,median 1.7 and range (0.1-3.1 and in controls mean was 0.8±0.3, median 0.8 and range (0.4-1.4.Comparison between each 2 groups as regards heparanase level was of high statistically significant difference, p value being (p<0.001 when comparing AML/ALL and AML/controls and (p=0.035 when comparing ALL/controls. Cut off value for heparanase gene was calculated using Roc curve and was found to be 1.413 with 80% sensitivity and 100% specificity. According to this cut off level, 20/20 (100% AML cases were heparanase positive, 12

  17. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; ZHANG Bin; Schmidhuber, Sabine; Yi, Sun-ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase i...

  18. Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

    2015-12-28

    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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

  19. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael;

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  20. Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate

    Abrahamsson, Jonas; Forestier, Erik; Heldrup, Jesper;

    2011-01-01

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.......To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course....

  1. MORPHOLOGIC & FLOWCYTOMETRIC ANALYSIS OF ACUTE LEUKEMIAS IN A TEACHING HOSPITAL IN CHHATTISGARH

    Rabia Parveen; Minal; Vanita; Patra; Swati

    2015-01-01

    BACKGROUND : Immunophenotyping of leukemi a by flowcytometry offers a better classification of the hematopoietic lineage of malignant cells as compared to morphology. AIM : To determine the immunophenotypic subtypes of acute leukemia in a tertiary care teaching hospital. MATERIAL & METHODS : A one y ear study of morphologic & flowcytometric data of patients with acute leukemia. RESULTS : Total numbers ...

  2. A Rare Case of Adult Acute Lymphoblastic Leukemia Presenting with Paraparesis and Multiple Osteolytic Lesions

    Verma, S P; Dubashi, B.; Basu, D; Dutta, T. K.; Kar, R.

    2013-01-01

    Acute lymphoblastic leukemia presenting with bone involvement and multiple osteolytic lesions has been commonly reported in pediatric population. Various myeloid and lymphoid malignancies can rarely present with bony lesions. We are reporting an adult female patient with acute lymphoblastic leukemia who presented with paraparesis and multiple osteolytic lesions in skull initially giving false impression of multiple myeloma.

  3. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia

    Hollink, Iris H. I. M.; van den Heuvel-Eibrink, Marry M.; Arentsen-Peters, Susan T. C. J. M.; Zimmermann, Martin; Peeters, Justine K.; Valk, Peter J. M.; Balgobind, Brian V.; Sonneveld, Edwin; Kaspers, Gertjan J. L.; de Bont, Eveline S. J. M.; Trka, Jan; Baruchel, Andre; Creutzig, Ursula; Pieters, Rob; Reinhardt, Dirk; Zwaan, C. Michel

    2011-01-01

    Background Dysfunctioning of CCAAT/enhancer binding protein alpha (C/EBP alpha) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but this m

  4. Analyses of karyotypic characteristics and prognosis in pediatric acute myeloblastic leukemia

    阮敏

    2012-01-01

    Objective Acute myeloblastic leukemia(AML) accounts for 15 to 25 percent of childhood acute leukemias. Cytogenetic information is important for diagnosis,classification and prognosis of AML. Our aim was to analyze the relationship between karyotypic characteristics and prognosis of childhood

  5. Diagnostic imaging of limbs in children with acute leukemia

    Objective: To evaluate X-ray and MRI features of limbs in childhood acute leukemia. Methods: Thirteen children with acute leukemia in our pediatric hematology ward were recruited. All patients were pathologically diagnosed by bone marrow aspiration and complained of bone or joint pain in the first visit. Conventional X-ray and MRI examinations of algesic sites were performed before clinical treatment and after complete remission. MR images were obtained with SE-T1WI, SE-T2WI and T2WI-fat suppressed sequences and symmetrical bilateralism was requested while scanning. X-ray and MRI manifestations were evaluated and compared. Results: All 13 patients had received X-ray examinations. Among them, 6 had normal X-ray findings, whereas the other 7 (14 sites) showed various abnormalities including radiolucent metaphyseal bands (5 sites), periosteal reaction (3 sites), osteapenia (2 sites), mixed lesions (lysis- sclerosis, 1 site), and permeative pattern (3 sites). The number of patients for MRI examinations was 8 (11 sites). Among them, 6 (9 sites) showed bone marrow infiltration and bone marrow necrosis accompanied by normal X-ray findings, another 2 (2 sites) showed bone marrow infiltration associated with radiographic abnormalities of periosteal reaction and radiolucent metaphyseal bands. Four cases were followed up within 1 week when reached complete remission by chemotherapy. MR images features included reduced sizes of bone marrow infiltration lesions associated with increased signal intensity on T1WI, and disappearance of double-line sign on bone marrow necrosis accompanied by signal homogenization. However, the radiograph before and after treatment in the same cases did not differ significantly. Conclusions: MRI was earlier and more comprehensive in showing limbs bone marrow abnormality than radiogram in acute leukemia children with chief complaint of osteoarticular pains. MRI might be one of indicators in following up therapeutic effect for AL children with

  6. Technical relapsed testicular irradiation for acute lymphoblastic leukemia

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  7. Management of Acute Myeloid Leukemia in the Intensive Care Setting.

    Cowan, Andrew J; Altemeier, William A; Johnston, Christine; Gernsheimer, Terry; Becker, Pamela S

    2015-10-01

    Patients with acute myeloid leukemia (AML) who are newly diagnosed or relapsed and those who are receiving cytotoxic chemotherapy are predisposed to conditions such as sepsis due to bacterial and fungal infections, coagulopathies, hemorrhage, metabolic abnormalities, and respiratory and renal failure. These conditions are common reasons for patients with AML to be managed in the intensive care unit (ICU). For patients with AML in the ICU, providers need to be aware of common problems and how to manage them. Understanding the pathophysiology of complications and the recent advances in risk stratification as well as newer therapy for AML are relevant to the critical care provider. PMID:24756309

  8. Transplantations in adult acute lymphoblastic leukemia--grounds for optimism?

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG Adult Acute Lymphoblastic Leukemia Study establishes the value of sibling donor allogeneic transplantation in patients with standard risk, demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor transplantations on this study protocol appear to do well and might establish the value of such an approach for those without a sibling. Reduced-intensity conditioning might begin to address the transplantation-related mortality problems of the older patients. The youngest adults might not need to undergo transplantation at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. PMID:19778843

  9. Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults.

    Ronson, Aharon; Tvito, Ariella; Rowe, Jacob M

    2016-06-01

    Patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis with less than 10 % of patients surviving 5 years. Most such patients cannot be rescued with currently available therapies, whatever the initial treatment they receive. Therefore, there is an urgent need for novel treatment options. Fortunately, over the past several years, an improved understanding of the biology of the disease has allowed the identification of rational molecular targets for therapeutic endeavors and the emergence of novel therapies has sparked great interest. This review will discuss the current treatment landscape for adult patients with relapsed and/or refractory ALL. PMID:27207612

  10. Comorbidity and performance status in acute myeloid leukemia patients

    Ostgård, L S G; Nørgaard, J M; Sengeløv, H;

    2015-01-01

    As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and World Health Organization Performance Status (PS......) on achievement of complete remission and mortality in all Danish AML patients treated between 2000 and 2012 overall and stratified by age. Comorbidity was measured using a modified version of the Charlson Comorbidity Index, with separate adjustment for pre-leukemic conditions. Of 2792 patients, 1467...

  11. Flow cytometric analysis of Mixed phenotype acute leukemia: Experience from a tertiary oncology center

    Renu Sukumaran

    2015-01-01

    Full Text Available Introduction: Mixed phenotype acute leukemia (MPAL is a rare subset of acute leukemia where the blasts exhibit lineage specific antigens of more than one lineage. Flow cytometric immunophenotyping is essential for the diagnosis of MPAL and the accurate diagnosis highly depends on the panel of markers used. The precise incidence of MPAL is uncertain as various institutions use different combinations of antibodies to assign the blasts to a particular lineage. Aim: The aim was to study the immunoprofile of acute leukemia including aberrant antigen expressions and to study the incidence, clinical features, laboratory findings, and immunophenotype of MPAL in our institution. Materials and Methods: All cases of acute leukemias in which flow cytometric analysis during 1-year period from July 2012 to July 2013 were included in this study. Results: During the study period, flow cytometric analysis of 506 cases was performed. B lymphoblastic leukemia was the most common subtype of acute leukemia. CD13 was the most common aberrant antigen expression in acute lymphoblastic leukemia and CD7 was the most common aberrant antigen expression in acute myeloid leukemia. A diagnosis of MPAL was made in 15 cases, which accounted for 2.96% of all leukemias. 9 cases were diagnosed as T/myeloid, 5 cases as B/myeloid and 1 case as B/T. Conclusion: Mixed phenotype acute leukemia is a rare subset of acute leukemia. Flow cytometry is critical in establishing a diagnosis of MPAL. The panel of antibodies used is important in the identification of the "mixed" phenotype. Cytoplasmic markers (cytoplasmic MPO, cytoplasmic 79a, cytoplasmic 22 and cytoplasmic CD3 should be included in the primary flow cytometric panel.

  12. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Xian-Ming Mo; Hong Xu; Ting-Ting Zeng; Neng-Gang Jiang; Yong-Qian Jia; Jing-Tao Dong; Jian-Hua Yu; Wen-Tong Meng

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7R alpha (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Anal...

  13. MORPHOLOGIC & FLOWCYTOMETRIC ANALYSIS OF ACUTE LEUKEMIAS IN A TEACHING HOSPITAL IN CHHATTISGARH

    Rabia Parveen

    2015-10-01

    Full Text Available BACKGROUND : Immunophenotyping of leukemi a by flowcytometry offers a better classification of the hematopoietic lineage of malignant cells as compared to morphology. AIM : To determine the immunophenotypic subtypes of acute leukemia in a tertiary care teaching hospital. MATERIAL & METHODS : A one y ear study of morphologic & flowcytometric data of patients with acute leukemia. RESULTS : Total numbers of acute leukemia patients diagnosed morphologically were 45, out of which 20 patients underwent immunophenotyping by flowcytometry. Maximum patients wer e in the age group of 0 - 10 yrs followed by 11 - 20 yrs with males outnumbering female. Immunophenotypically they belonged to ALL - B cell lineage, ALL - T cell lineage, AML, biphenotypic, inconclusive. CONCLUSION : Immunophenotyping of acute leukemias by flowcyto metry, not only helps to confirm the morphologic diagnosis but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia

  14. Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

    Jianbiao; Zhou; Wee-Joo; Chng

    2014-01-01

    Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

  15. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  16. Emerging role for microRNAs in acute promyelocytic leukemia.

    Nervi, C; Fazi, F; Rosa, A; Fatica, A; Bozzoni, I

    2007-01-01

    Hematopoiesis is highly controlled by lineage-specific transcription factors that, by interacting with specific DNA sequences, directly activate or repress specific gene expression. These transcription factors have been found mutated or altered by chromosomal translocations associated with leukemias, indicating their role in the pathogenesis of these malignancies. The post-genomic era, however, has shown that transcription factors are not the only key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, posttranslational modifications of histones, remodeling of nucleosomes, and expression of small regulatory RNAs all contribute to the regulation of gene expression and determination of cell and tissue specificity. Deregulation ofthese epigenetic mechanisms cooperates with genetic alterations to the establishment and progression of tumors. MicroRNAs (miRNAs) are negative regulators of the expression of genes involved in development, differentiation, proliferation, and apoptosis. Their expression appears to be tissue-specific and highly regulated according to the cell's developmental lineage and stage. Interestingly, miRNAs expressed in hematopoietic cells have been found mutated or altered by chromosomal translocations associated with leukemias. The expression levels of a specific miR-223 correlate with the differentiation fate of myeloid precursors. The activation of both pathways of transcriptional regulation by the myeloid lineage-specific transcription factor C/EBPalpha (CCAAT/enhancer-binding protein-alpha), and posttranscriptional regulation by miR-223 appears essential for granulocytic differentiation and clinical response of acute promyelocytic leukemia (APL) blasts to all-trans retinoic acid (ATRA). Together, this evidence underlies transcription factors, chromatin remodeling, and miRNAs as ultimate determinants for the correct organization of cell type-specific gene arrays and hematopoietic differentiation, therefore providing new

  17. Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia

    Judith E Karp

    2008-09-01

    Full Text Available Judith E Karp1, Jeffrey E Lancet21Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA; 2H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, USAAbstract: Farnesyltransferase inhibitors (FTIs represent a new class of signal transduction inhibitors that block the processing of cellular polypeptides that have cysteine terminal residues and, by so doing, interdict multiple pathways involved in proliferation and survival of diverse malignant cell types. Tipifarnib is an orally bioavailable, nonpeptidomimetic methylquinolone FTI that has exhibited clinical activity in patients with myeloid malignancies including elderly adults with acute myelogenous leukemia (AML who are not candidates for traditional cytotoxic chemotherapy, patients with high-risk myelodysplasia, myeloproliferative disorders, and imatinib-resistant chronic myelogenous leukemia. Because of its relatively low toxicity profile, tipifarnib provides an important alternative to traditional cytotoxic approaches for elderly patients who are not likely to tolerate or even benefit from aggressive chemotherapy. In this review, we will focus on the clinical development of tipifarnib for treatment of newly diagnosed AML, both as induction therapy for elderly adults with poor-risk AML and as maintenance therapy following achievement of first complete remission following induction and consolidation therapies for poor-risk AML. As with all other malignancies, the optimal approach is likely to lie in rational combinations of tipifarnib with cytotoxic, biologic and/or immunomodulatory agents with non-cross-resistant mechanisms of action. Gene expression profi ling has identified networks of differentially expressed genes and gene combinations capable of predicting response to single agent tipifarnib. The clinical and correlative laboratory trials in progress and under development will provide the critical foundations for

  18. A novel karyotype in acute myeloid leukemia with basophilia.

    Servitzoglou, Marina; Grenzelia, Maria; Baka, Margarita; Harisi, Marietta; Pourtsidis, Apostolos; Bouhoutsou, Despina; Varvoutsi, Maria; Doganis, Dimitrios; Dana, Helen; Divane, Aspasia; Kosmidis, Helen

    2014-03-01

    Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, -21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity. PMID:24552500

  19. Evolving Therapies in Acute Myeloid Leukemia: Progress at Last?

    DeAngelo, Daniel J; Stein, Eytan M; Ravandi, Farhad

    2016-01-01

    Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials. The revolution in understanding the genetics of AML, facilitated by next-generation sequencing, has led to many new drugs against driver mutations. Better methods of identification of leukemic blasts have provided us with better means to detect the disease left behind after cytotoxic chemotherapy regimens. This measurable residual disease has been correlated with poorer relapse-free survival, demonstrating the need for novel strategies to eradicate it to improve the outcome of patients with acute leukemias. In this article, we discuss adapting and improving AML therapy by age and comorbidities, emerging targeted therapies in AML, and minimal residual disease (MRD) assessment in AML. PMID:27249736

  20. Treatment of Acute Lymphoblastic Leukemia from Traditional Chinese Medicine

    Ya-Li Hsiao

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR, an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs inhibit the thymidylate synthase (TS. Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment.

  1. Fanconi Syndrome: A Rare Initial Presentation of Acute Lymphoblastic Leukemia.

    Sahu, Kamal Kant; Law, Arjun Datt; Jain, Nidhi; Khadwal, Alka; Suri, Vikas; Malhotra, Pankaj; Varma, Subhash Chander

    2016-06-01

    A-14-year old boy, presented with a short history of excessive thirst and increased urine output. Clinical examination showed pallor, generalized lymphadenopathy and hepatosplenomegaly. For evaluation of his polyuric state he underwent routine laboratory investigations, including renal function test, acid-base studies, urine analysis. Blood tests suggested hypokalemia, hypouricemia, hypocalcemia and hyperchloremia with normal liver and kidney function tests. The arterial blood gas analysis was suggestive of normal anion gap metabolic acidosis. Urine analysis was suggestive of hyperuricosuria, hypercalciuria and glycosuria with a positive urine anion gap. His hemogram showed pancytopenia with differential count showing 88% blasts. Bone marrow examination and flowcytometry confirmed the diagnosis of B cell acute lymphoblastic leukemia. Hence this case was atypical and very interesting in the sense that the Fanconi syndrome is very rare to be an initial presenting feature of acute lymphoblastic leukemia. The patient was started on oral as well intravenous supplementation with potassium, bicarbonate, calcium and phosphorus. Simultaneously, as per the modified BFM -90 protocol (four drug based regimen-Prednisolone, vincristine, daunorubicin, cyclophosphamide along with l-asparaginase), he was started on induction protocol. By the end of 3rd week of induction therapy, his urine output started normalizing and finally settled at the end of induction therapy. At present he is in the maintenance phase of chemotherapy. PMID:27408343

  2. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  3. Loss of TAL-1 protein activity induces premature apoptosis of Jurkat leukemic T cells upon medium depletion.

    Leroy-Viard, K; Vinit, M A; Lecointe, N; JOUAULT, H.; Hibner, U; Roméo, P H; Mathieu-Mahul, D

    1995-01-01

    Transcriptional activation of the tal-1 gene occurs in -30% of patients with T cell Acute Lymphoblastic Leukemia and is therefore likely to be involved in human T cell leukemogenesis. However, the TAL-1 protein functional properties involved in this process have not been assessed so far. We have derived a clonal subline of the Jurkat T cell line which produced solely a mutant truncated form of TAL-1 protein. Sequencing of genomic DNA and cDNAs showed that the only transcribed tal-1 allele of ...

  4. Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia

    Sushma Belurkar

    2013-01-01

    Full Text Available Introduction: The classification of acute leukemias has revolutionized over the years. Immunophenotyping of acute leukemia has gained popularity because of its influence on treatment and prognosis of the disease. The various antigens expressed by the leukemic cells can be assessed by flowcytometry (FCA and can be used in rendering specific treatment and predicting the outcome of the different types of acute leukemia. Aims: The main aim of this study was to compare the morphologic and cytochemical diagnoses with flowcytometric diagnoses in acute leukemia and to analyze the usefulness of FCA over morphology. Results: In this study we analyzed 50 cases of acute leukemia and found concordance rate as high as 86% between morphologic/cytochemical diagnosis and flowcytometric diagnosis. Of these, complete concordance was seen in 58% of the cases and partial concordance was seen in 22% of the cases. Non-concordance was seen in only 4% of our cases. In remaining 16% of our cases FCA helped in sub classifying the acute leukemia where morphology and cytochemistry had failed to do so. CD19 and 20 were found to be consistent B-cell markers and CD3 was a very specific marker for T-cell leukemia. CD13 and 33 were important myeloid markers and were aided by other secondary panel of markers like CD14, CD117 and CD41. Conclusion: FCA not only helps in confirming morphologic diagnosis in acute leukemia but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia. Immunophenotyping is of utmorst importance in classifying acute leukemia as it greatly influences the treatment and the prognosis.

  5. Aleukemic Leukemia Cutis Manifesting with Disseminated Nodular Eruptions and a Plaque Preceding Acute Monocytic Leukemia: A Case Report

    Yonal, Ipek; Hindilerden, Fehmi; Coskun, Raif; Dogan, Oner Ibrahim; Nalcaci, Meliha

    2011-01-01

    Aleukemic leukemia cutis (ALC), a discrete tumor of leukemic cells involving the skin, may be the first manifestation of acute myeloid leukemia, preceding the onset in marrow and blood by months and years. ALC is often difficult to diagnose and is associated with a dismal prognosis. A 63-year-old male presented with nodular swellings on the face, a plaque extending over the right shoulder and multiple enlarged cervical lymph nodes. The skin biopsy of the plaque lesion showed a diffuse neoplastic infiltration extending from the dermis to subcutaneous tissue with diffuse positivity for myeloperoxidase and focal positivity for CD34 on immunohistochemical staining. The diagnosis was leukemia cutis. One month later, acute monocytic leukemia (FAB AML-M5b) was diagnosed. The patient died on the seventh month of diagnosis. PMID:22187541

  6. ADAMTS2 gene dysregulation in T/myeloid mixed phenotype acute leukemia

    Tota, Giuseppina; Coccaro, Nicoletta; Zagaria, Antonella; Anelli, Luisa; Casieri, Paola; Cellamare, Angelo; Minervini, Angela; Minervini, Crescenzio Francesco; Brunetti, Claudia; Impera, Luciana; Carluccio, Paola; Cumbo, Cosimo; Specchia, Giorgina; Albano, Francesco

    2014-01-01

    Background Mixed phenotype acute leukemias (MPAL) include acute leukemias with blasts that express antigens of more than one lineage, with no clear evidence of myeloid or lymphoid lineage differentiation. T/myeloid (T/My) MPAL not otherwise specified (NOS) is a rare leukemia that expresses both T and myeloid antigens, accounting for less than 1% of all leukemias but 89% of T/My MPAL. From a molecular point of view, very limited data are available on T/My MPAL NOS. Case presentation In this re...

  7. Immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia and mumps.

    Kurekci, A Emin; Atay, A Avni; Demirkaya, Erkan; Sarici, S Umit; Ozcan, Okan

    2006-03-01

    Immune thrombocytopenic purpura in childhood is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child. In children it usually follows a viral infection (eg, mumps, rubella) or immunization. We report for the first time a child with acute lymphoblastic leukemia who developed immune thrombocytopenic purpura due to mumps during the maintenance phase of acute lymphoblastic leukemia treatment. PMID:16679943

  8. Clinical Study of Acute Mixed-lineage Leukemia in 14 Children

    Yaodong Zhang; Lina Tan; Xiaoling Zhang; Haiyan Wei; Qun Hu

    2011-01-01

    Objective: Acute mixed-lineage leukemia (AMLL) is characterized as the acute leukemia involved with acute myeloid cells and lymphoid cells at the same time. The AMLL is easily misdiagnosed because of a dual character involved with lymphoid and myeloid cells. At present, researches of AMLL in adults are more common. Only some are reported for children. Therefore, our aim was to study clinical characteristics of the childhood AMLL.Methods: From January 2000 to July 2009, 14 cases of AMLL childr...

  9. CD117 expression on blast cells in acute myeloid leukemia

    Goryainova N.V.

    2015-09-01

    Full Text Available The aim of the present work was to analyze the frequency of CD117 (c-KIT antigen expression on the blast cells in acute myeloid leukemia (AML, evaluation of the presence of the relationship between the expression of the c-KIT and leukemia according to the FAB classification and definition of co-expression of the antigen CD117, antigens CD33 and CD34. The data of 47 patients with AML were diagnosed. M0 AML variant was established in 3 (6% patients, M1 – in 2 (4%, M2 – in 9 (20%, M4 – in 22 (47% and M5 – in 11 (23%. For immunophenotypic stu¬dies monoclonal antibodies (mAb that detect antigens of anti-CD34, anti-CD33 and anti-CD117 (Becton Dickinson, USA were used. The presence of the antigen CD117 was detected in 39 people, accounting for 83% of all surveyed. Antigen c-KIT was present in 48.117.0% cells on average: in all 3 cases – AML M0, in2 cases of AML M1, in 6 cases – AML M2, 20 of 22 cases – AML M4 and in 8 of 11 AML M5 cases. Average levels of CD117 in investigated leukemia cases statistically differed significantly (p=0.0067. Among 39 CD117- positive patients in 25 (53% co-expression of CD117+/CD34+ was revealed. Expression of CD117+/CD34- was observed in 14 cases (30%, CD117-/CD34+ – in 4 cases (8,5%, CD117-/CD34- – in 4 cases (8.5%. CD34 had of 64% of cells of myeloid origin. A high positive cor¬relation between expression of CD117 and CD34 (r=+0,5169 was determined, being statistically significant (p0,0067.

  10. [Recent Advances of Research on CEBPA Mutation in Acute Myeloid Leukemia].

    Yu, Wen-Qing; Sun, Jing-Nan; Tan, Ye-Hui; Cui, Jiu-Wei; Li, Wei

    2015-12-01

    CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment. PMID:26708912

  11. Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia

    Grossmann, Vera; Kern, Wolfgang; Harbich, Stefan; Alpermann, Tamara; Jeromin, Sabine; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten; Kohlmann, Alexander

    2011-01-01

    The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no muta...

  12. Targeting Suppressor of Variegation 3-9 Homologue 2 (SUV39H2 in Acute Lymphoblastic Leukemia (ALL

    Martin Mutonga

    2015-10-01

    Full Text Available Although recent progress in understanding the biology and optimizing the treatment of acute lymphoblastic leukemia (ALL has improved cure rates of childhood ALL to nearly 90%, the cure rate in adult ALL remains less than 50%. The poor prognosis in adult ALL has in part been attributed to larger proportion of high-risk leukemia showing drug resistance. Thus, identifying novel therapeutic targets in ALL is needed for further improvements in treatment outcomes of adult ALL. Genetic aberration of chromatin-modifying molecules has been recently reported in subtypes of ALL, and targeting components of chromatin complexes has shown promising efficacy in preclinical studies. Suppressor of variegation 3-9 homologue 2 (SUV39H2, also known as KMT1B, is a SET-domain–containing histone methyltransferase that is upregulated in solid cancers, but its expression is hardly detectable in normal tissues. Here, we show that SUV39H2 is highly expressed in ALL cells but not in blood cells from healthy donors and also that SUV39H2 mRNA is expressed at significantly higher levels in bone marrow or blood cells from patients with ALL obtained at diagnosis compared with those obtained at remission (P = .007. In four ALL cell lines (Jurkat and CEM derived from T-ALL and RS4;11 and REH derived from B-ALL, SUV39H2 knockdown resulted in a significant decrease in cell viability (~77%, P < .001, likely through induction of apoptosis. On the other hand, SUV39H2 overexpression made cells more resistant to chemotherapy. We conclude that SUV39H2 is a promising therapeutic target and further investigation of this therapeutic approach in ALL is warranted.

  13. Problems of prophylactic CNS radiotherapy in acute children's leukemia

    The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

  14. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Yadollah Zahedpasha

    2011-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.Case Presentation: This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didnt have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.Conclusion: The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.

  15. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  16. Microenvironmental cues for T-cell acute lymphoblastic leukemia development.

    Passaro, Diana; Quang, Christine Tran; Ghysdael, Jacques

    2016-05-01

    Intensive chemotherapy regimens have led to a substantial improvement in the cure rate of patients suffering from T-cell acute lymphoblastic leukemia (T-ALL). Despite this progress, about 15% and 50% of pediatric and adult cases, respectively, show resistance to treatment or relapse with dismal prognosis, calling for further therapeutic investigations. T-ALL is an heterogeneous disease, which presents intrinsic alterations leading to aberrant expression of transcription factors normally involved in hematopoietic stem/progenitor cell development and mutations in genes implicated in the regulation of cell cycle progression, apoptosis, and T-cell development. Gene expression profiling allowed the classification of T-ALL into defined molecular subgroups that mostly reflects the stage of their differentiation arrest. So far this knowledge has not translated into novel, targeted therapy. Recent evidence points to the importance of extrinsic signaling cues in controlling the ability of T-ALL to home, survive, and proliferate, thus offering the perspective of new therapeutic options. This review summarizes the present understanding of the interactions between hematopoietic cells and bone marrow/thymic niches during normal hematopoiesis, describes the main signaling pathways implicated in this dialog, and finally highlights how malignant T cells rely on specific niches to maintain their ability to sustain and propagate leukemia. PMID:27088913

  17. Current management of newly diagnosed acute promyelocytic leukemia.

    Cicconi, L; Lo-Coco, F

    2016-08-01

    The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease. PMID:27084953

  18. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  19. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects

  20. Two cases of intracerebral calcification in childhood acute leukemia

    Two children with acute lynphocytic leukemia (ALL) had intracerebral calcifications. The first case was a girl diagnosed as ALL in her seventh month. She developed two episodes of meningeal leukemia. She was treated by intrathecal methotrexate (MTX) and 19.80 Gy of whole-brain irradiation. Three months after irradiation, CT revealed low-density areas around both the lateral ventricles, especially at the anterior horns, suggesting necrotizing leukoencephalopathy. Seven months after irradiation, CT revealed bilateral gyriform calcifications of both cerebral hemispheres. The second case was a boy diagnosed as ALL at 1.5 years old. He was treated by prop hylactic intrathecal MTX and 24.00 Gy of whole-brain irradiation. Fourteen months after irradiation, CT revealed multiple small punctated calcifications of both cerebral hemispheres. The combination of whole-brain irradiation with MTX therapy was perhaps the cause of the high incidence of these calcifications, because the irradiation doses in these cases were too small to cause these injuries. (author)

  1. Hematopoietic Differentiation Is Required for Initiation of Acute Myeloid Leukemia.

    Ye, Min; Zhang, Hong; Yang, Henry; Koche, Richard; Staber, Philipp B; Cusan, Monica; Levantini, Elena; Welner, Robert S; Bach, Christian S; Zhang, Junyan; Krivtsov, Andrei V; Armstrong, Scott A; Tenen, Daniel G

    2015-11-01

    Mutations in acute myeloid leukemia (AML)-associated oncogenes often arise in hematopoietic stem cells (HSCs) and promote acquisition of leukemia stem cell (LSC) phenotypes. However, as LSCs often share features of lineage-restricted progenitors, the relative contribution of differentiation status to LSC transformation is unclear. Using murine MLL-AF9 and MOZ-TIF2 AML models, we show that myeloid differentiation to granulocyte macrophage progenitors (GMPs) is critical for LSC generation. Disrupting GMP formation by deleting the lineage-restricted transcription factor C/EBPa blocked normal granulocyte formation and prevented initiation of AML. However, restoring myeloid differentiation in C/EBPa mutants with inflammatory cytokines reestablished AML transformation capacity. Genomic analyses of GMPs, including gene expression and H3K79me2 profiling in conjunction with ATAC-seq, revealed a permissive genomic environment for activation of a minimal transcription program shared by GMPs and LSCs. Together, these findings show that myeloid differentiation is a prerequisite for LSC formation and AML development, providing insights for therapeutic development. PMID:26412561

  2. G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound

    Cabrera, Maia; Gomez, Natalia; Remes Lenicov, Federico; Echeverría, Emiliana; Shayo, Carina; Moglioni, Albertina; Fernández, Natalia; Davio, Carlos

    2015-01-01

    Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4’-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic ...

  3. Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid

    Jain Ankit

    2009-06-01

    Full Text Available Radioactive iodine (RAI therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

  4. Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid

    Jain Ankit; Premalata CS; Saini KV; Bapsy PP; Sajeevan KV; Tejinder Singh; Ullas Batra; Babu Govind; Lokanatha Dasappa; Suresh Atilli; Permeshwar R

    2009-01-01

    Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

  5. Incidence of Acute Myeloid Leukemia in Children in Haji Adam Malik Hospital Medan

    Nafianti, Selvi; Rosdiana, Nelly; Lubis, Bidasari

    2010-01-01

    Background: Leukemia is the most common malignancy in childhood and about 15 percent of childhood leukemia cases are acute myelogenous leukemia (AML). It is reported in more than 13,000 people newly diagnosed each year. The overall survival rate has reached a plateau at approximately 60%, suggesting that further intensification of therapy per se will not substantially improve survival rates. Methods: This study was retrospective with all the children who came to Division Hematology-Oncology H...

  6. Successful treatment with interferon of chicken pox in children with acute leukemia.

    Kim, Byung Soo

    1984-01-01

    Childhood leukemia, especially acute lymphocytic leukemia, can now be completely cured by a multimodality approach in one out of every two patients. Since prolonged maintenance therapy with anti-cancer agents for three years is required for complete cure, a significant problem during this course of treatment is death due to secondary infection. Those with childhood leukemia receiving anti-cancer chemotherapy who became secondarily injected with chicken pox can now be treated successfully with...

  7. Mixed Phenotype Acute Leukemia with Low Hypodiploidy in a Pediatric Patient

    Salazar, Elizabeth G.; Wertheim, Gerald B.; Biegel, Jaclyn A.; Hwang, William; Tasian, Sarah K.; Rheingold, Susan R.

    2015-01-01

    We describe the case of a 16 year-old female with mixed phenotype acute leukemia B/myeloid, NOS (formerly biphenotypic leukemia) with masked hypodiploidy and somatic TP53 and CDKN2A/B deletions. She achieved morphologic remission with lymphoid-directed multi-agent chemotherapy, but experienced an early medullary relapse 11 months from initial diagnosis. Her case details the unusual finding of hypodiploidy in a patient with ambiguous lineage leukemia and highlights the complexity of therapy se...

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

    Ishii, Kazusa; Barrett, Austin J

    2016-02-01

    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

  9. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child

  10. Acute lymphoblastic leukemia in children with Down syndrome

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin;

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995......(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the...

  11. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    Pharmacogenetics covers the genetic variation affecting pharmacokinetics and pharmacodynamics. and their influence on drug-response phenotypes. The genetic variation includes an estimated 15 million single nucleotide polymorphisms (SNP) and is a key determinator for the interindividual differences...... treatment response. In the future, high-throughput, low-cost, genetic platforms will allow screening of hundreds or thousands of targeted SNPs to give a combined gene-dosage effect ( = individual SNP risk profile), which may allow pharmacogenetic-based individualization of treatment Udgivelsesdato: 2008/11...... in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids...

  12. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

    Harsh Shah

    2015-01-01

    Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  13. Prediction of intellectual deficits in children with acute lymphoblastic leukemia

    Trautman, P.D.; Erickson, C.; Shaffer, D.; O' Connor, P.A.; Sitarz, A.; Correra, A.; Schonfeld, I.S.

    1988-06-01

    Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed.

  14. Brain damage after treatment for acute lymphoblastic leukemia

    In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors. (orig.)

  15. Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy

    Gaurav Prakash

    2012-01-01

    Full Text Available Angioinvasive pulmonary infection from filamentous fungi is not an uncommon occurrence in immunocompromised patients like acute lymphoblastic leukemia (ALL. Rarely, these lesions can spread via the hematogenous route and involve multiple visceral organs. We report a case of a 14-year-old boy with ALL who developed angioinvasive pulmonary aspergillosis early in the course of induction therapy, which was followed by hematogenous dissemination and formation of multiple brain abscesses. The patient was treated with intravenous amphotericin B. There was no response to the therapy and the patient succumbed to disseminated infection. Postmortem lung biopsy confirmed angioinvasive pulmonary aspergillosis. Poor penetration of amphotericin B across the blood-brain barrier could be one of the contributory factors for poor response to antifungal therapy. We discuss the various antifungal agents with respect to their penetration in brain.

  16. Splenic microabscesses in patients with acute myelogenous leukemia

    Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy got septic fever. Fever was unresponsive to broad-spectrum antibiotic therapy. Ultrasonography showed multiple 0,5-2 cm in diameter, anechoic densities and some 1-3 cm ''target'' appearances in spleen and liver. Computed tomography demonstrated multiple, round, 0,5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma. These microabscesses increased in size and number of lesions without equivalent antifungal therapy and decreased or disappeared after specific treatment. Candida-infection was assured by histologic liver specimen in four patients, fungal organisms were seen microscopically in liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lungand CNS. (orig.)

  17. Bacteremia due to Aeromonas hydrophila in Acute Lymphoblastic Leukemia

    Aeromonas hydrophila (A. hydrophila) is a low virulent organism but may cause devastating fatal infections in immunocompromised host especially in liver cirrhosis. It is rarely reported to cause septicemia in a patient with Acute Lymphoblastic Leukemia (ALL). The mortality rate of septicemia due to A. hydrophila is 29% to 73%. We report a case of 59-year-old female patient who was a known case of ALL, presented with the complaints of fever, lethargy and generalized weakness for one month. After taking blood samples for investigations, empirical antimicrobial therapy was started. She did not improve after 48 hours of therapy. Meanwhile blood culture revealed pure growth of A. hydrophila. After sensitivity report was available, ciprofloxacin was started. Patient became afebrile after 48 hours of treatment with ciprofloxacin. It is very vital to correctly identified and treat bacteremia due to A. hydrophila especially in the underlying leukemic patient. (author)

  18. Prediction of intellectual deficits in children with acute lymphoblastic leukemia

    Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed

  19. Side effect of cranial radiation in childhood acute leukemia, 1

    We examined the somnolence syndrome, which is one of the side effects of cranial irradiation. Out of 53 patients in acute leukemia who had received cranial irradiation, nine patients (17%) developed the somnolence syndrome. Patients with the somnolence syndrome showed slow waves on EEG. Some patients had ventricular dilatation and widening of sulci before cranial irradiation on CT findings, but these findings improved after cranial irradiation. Out of nine cases with the somnolence syndrome, 6 patients survived and did not experience difficulties in school. But one patient showed calcification on CT brain scan. It is considered that the cause of the somnolence syndrome is a trasient inhibition of myelin synthesis and most patients improved without serious sequelae. It is necessary to follow up many cases of somnolence syndrome. (author)

  20. Invasive fungal diseases in patients with acute lymphoid leukemia.

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  1. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  2. /sup 32/P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

    Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

    1978-08-01

    In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi /sup 32/P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of /sup 32/P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to /sup 32/P. The exposed population should be closely followed, since this will likely permit assessment of the risk of /sup 32/P-induced leukemia in a nonneoplastic condition.

  3. Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

    Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía; Roman, Eve; Schüz, Joachim; Magnani, Corrado; Mora, Ana Maria; Mueller, Beth A; de Oliveira, Maria S Pombo; Dockerty, John D; McCauley, Kathryn; Lightfoot, Tracy; Hatzipantelis, Emmanouel; Rudant, Jérémie; Flores-Lujano, Janet; Kaatsch, Peter; Miligi, Lucia; Wesseling, Catharina; Doody, David R; Moschovi, Maria; Orsi, Laurent; Mattioli, Stefano; Selvin, Steve; Kang, Alice Y; Clavel, Jacqueline

    2016-08-15

    The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases. PMID:27492895

  4. Targeting Leukemia Stem Cells in vivo with AntagomiR-126 Nanoparticles in Acute Myeloid Leukemia

    Dorrance, Adrienne M.; Neviani, Paolo; Ferenchak, Greg J.; Huang, Xiaomeng; Nicolet, Deedra; Maharry, Kati S.; Ozer, Hatice G; Hoellarbauer, Pia; Khalife, Jihane; Hill, Emily B.; Yadav, Marshleen; Bolon, Brad N.; Lee, Robert J.; Lee, L.James; Croce, Carlo M.; Garzon, Ramiro; Caligiuri, Michael A.; Bloomfield, Clara D.; Marcucci., Guido

    2015-01-01

    Current treatments for acute myeloid leukemia (AML) are designed to target rapidly dividing blast populations with limited success in eradicating the functionally distinct leukemia stem cell (LSC) population, which is postulated to be responsible for disease resistance and relapse. We have previously reported high miR-126 expression levels to be associated with a LSC-gene expression profile. Therefore, we hypothesized that miR-126 contributes to “stemness” and is a viable target for eliminating the LSC in AML. Here we first validate the clinical relevance of miR-126 expression in AML by showing that higher expression of this microRNA (miR) is associated with worse outcome in a large cohort of older (≥60 years) cytogenetically normal AML patients treated with conventional chemotherapy. We then show that miR-126 overexpression characterizes AML LSC-enriched cell subpopulations and contributes to LSC long-term maintenance and self-renewal. Finally, we demonstrate the feasibility of therapeutic targeting of miR-126 in LSCs with novel targeting nanoparticles (NP) containing antagomiR-126 resulting in in vivo reduction of LSCs likely by depletion of the quiescent cell subpopulation. Our findings suggest that by targeting a single miR, i.e., miR-126, it is possible to interfere with LSC activity, thereby opening potentially novel therapeutic approaches to treat AML patients. PMID:26055302

  5. Therapeutic Effects of Myeloid Cell Leukemia-1 siRNA on Human Acute Myeloid Leukemia Cells

    Hadi Karami

    2014-05-01

    Full Text Available Purpose: Up-regulation of Mcl-1, a known anti-apoptotic protein, is associated with the survival and progression of various malignancies including leukemia. The aim of this study was to explore the effect of Mcl-1 small interference RNA (siRNA on the proliferation and apoptosis of HL-60 acute myeloid leukemia (AML cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative mRNA and protein expressions were quantified by quantitative real-time PCR and Western blotting, respectively. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of Mcl-1 siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using ELISA cell death assay. Results: Mcl-1 siRNA clearly lowered both Mcl-1 mRNA and protein levels in a time-dependent manner, leading to marked inhibition of cell survival and proliferation. Furthermore, Mcl-1 down-regulation significantly enhanced the extent of HL-60 apoptotic cells. Conclusion: Our results suggest that the down-regulation of Mcl-1 by siRNA can effectively trigger apoptosis and inhibit the proliferation of leukemic cells. Therefore, Mcl-1 siRNA may be a potent adjuvant in AML therapy.

  6. Cord blood transplantation for the treatment of acute leukemia

    Meerim Park; Young-ho Lee

    2013-01-01

    Objective This review discussed the available data on treatment outcomes of cord blood transplantation (CBT) for acute leukemia.Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed.Study selection We reviewed the articles of clinical results from various registries and institutions,as well as our experiences with CBT in children,adolescents and adults.Results This research has clearly shown that cord blood (CB) has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells.The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment,extending access,and examining outcomes in specific subgroups of patients.Many approaches have been investigated in the attempt to improve engraftment and survival.Variable factors have been identified,such as factors related to donor choice (human leukocyte antigen (HLA) compatibility,cell dose,and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimen).Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical.Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation.Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

  7. Clinico-hematological profile in biphenotypic acute leukemia

    S Gujral

    2009-01-01

    Full Text Available Background : We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL. Aim : Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude′s and the EGIL′s criteria have been compared for their diagnostic and clinical relevance. Material and Methods : Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia′s (EGIL′s scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. Results : There were 32 patients diagnosed with BAL, based on EGIL′s criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases followed by T-Myeloid BAL (13 cases were the commonest subtypes. Polymorphous population of blasts (16 cases was commonly associated with T-Myeloid BAL (10 cases. BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases. Fifteen patients received chemotherapy; eight achieved complete remission (CR at the end of the induction period. Conclusions : Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude′s criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML in blast crisis with biphenotypic expression and treated accordingly.

  8. PROGNOSTIC VALUE OF BRAIN AND ACUTE LEUKEMIA CYTOPLASMIC GENE EXPRESSION IN EGYPTIAN CHILDREN WITH ACUTE MYELOID LEUKEMIA

    adel abd elhaleim hagag

    2015-04-01

    Full Text Available Abstract      Background: Acute myeloid leukemia (AML accounts for 25%-35% of the acute leukemia in children. BAALC (Brain and Acute Leukemia, Cytoplasmic gene is a recently identified gene on chromosome 8q22.3 that has prognostic significance in AML.  The aim of this work was to study the impact of BAALC gene expression on prognosis of AML in Egyptian children. Patients and methods: This study was conducted on 40 patients of newly diagnosed AML who were subjected to the following: Full history taking, clinical examination, laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry and immunophenotyping, assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results: BAALC gene expression showed positive expression in 24 cases (60% and negative expression in 16 cases (40%. Patients who showed positive BAALC gene expression included 10 patients achieved complete remission, 8 patients died and 6 relapsed patients, while patients who showed negative expression include 12 patients achieved complete remission, 1 relapsed patient and 3 patients died. There was significant association between BAALC gene expression and FAB classification of patients of AML patientsas positive BAALC expression is predominantly seen in FAB subtypes M1 and M2 compared with negative BAALC gene expression that was found more in M3 and M4 (8 cases with M1, 12 cases with M2, 1 case with M3 and 3 cases with M4 in positive BAALC expression versus 2 cases with M1, 3 cases with M2, 4 cases with M3 and 7 cases with M4 in BAALC gene negative expression group with significant difference regarding FAB subtypes. As regard age, sex, splenomegaly, lymphadenopathy, pallor, purpura, platelets count, WBCs count, and percentage of blast cells in BM, the present study showed no significant association with BAALC. Conclusion: BAALC expression is an important prognostic factor in AML

  9. Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

    ESPíRITO SANTO, ANA ESPÍRITO; CHACIM, SÉRGIO; FERREIRA, ISABEL; LEITE, LUÍS; MOREIRA, CLAUDIA; PEREIRA, DULCINEIA; DANTAS BRITO, MARGARIDA DANTAS; NUNES, MARTA; DOMINGUES, NELSON; OLIVEIRA, ISABEL; MOREIRA, ILÍDIA; MARTINS, ANGELO; VITERBO, LUÍSA; MARIZ, JOSÉ MÁRIO; MEDEIROS, RUI

    2016-01-01

    Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (PAML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (PAML and those with de novo AML (P=0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P=0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients.

  10. Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells

    Dickson, Mark A.; Papadopoulos, Esperanza B.; Hedvat, Cyrus V.; Jhanwar, Suresh C.; Brentjens, Renier J.

    2014-01-01

    During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell...

  11. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  12. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  13. Estimation of plasma concentrations of hepatocyte growth factor in acute leukemia in Upper Egypt

    Ahmed E. Ahmed

    2015-03-01

    Conclusion: The results of the present study suggest that high plasma HGF may play a significant role in the leukemia process and contribute to the leukemic cell dissemination. The clinical significance of the increased level of HGF in acute leukemia needs further investigation and may suggest a novel therapeutic approach in this disease.

  14. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  15. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    Andersson, Anna K; Ma, Jing; Wang, Jianmin;

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  16. Glioblastoma multiforme in a child with acute lymphoblastic leukemia: Case report and review of literature

    Shah Kirit

    2004-07-01

    Full Text Available An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.

  17. Conservative Management of Pancreatic Pseudocysts in Children with Acute Lymphoblastic Leukemia

    Spraker, Holly L.; Spyridis, Georgios P.; Pui, Ching-Hon; Howard, Scott C.

    2009-01-01

    Treatment with asparaginase for acute lymphoblastic leukemia (ALL) can cause acute pancreatitis. Complication of pancreatitis by pancreatic pseudocyst formation can prolong the hospital stay, delay chemotherapy, and necessitate long-term parenteral nutrition. We report five children with ALL who developed acute pancreatitis complicated by pancreatic pseudocysts. They required modifications to their chemotherapy regimen and prolonged parenteral nutrition but no surgical intervention. All five ...

  18. Bone marrow transplantation in aplastic anemia, acute leukemia and solid tumors

    Results of bone marrow transplantation for the treatment of aplastic anemia, acute leukemia and solid tumors in the first 141 patients treated between September 1973 and January 1980 are reviewed. Preparation for transplantation with total body irradiation is described. (Auth.)

  19. The controversy of varicella vaccination in children with acute lymphoblastic leukemia

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre;

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered ...

  20. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

    2009-01-01

    Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant pr

  1. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi;

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared with...

  2. Imaging of liver and spleen candidiasis in patients with acute leukemia

    Seino, Yasuo; Tamakawa, Y.; Kato, T.; Kimura, Y.; Miyazaki, S.; Miura, R.; Ishida, H.

    1988-01-01

    Four patients with acute leukemia were found to have candidal abscess of liver and spleen. CT and US showed hepatosplenomegaly and microabscess. These findings might be useful in diagnosis of visceral candidiasis.

  3. Imaging of liver and spleen candidiasis in patients with acute leukemia

    Four patients with acute leukemia were found to have candidal abscess of liver and spleen. CT and US showed hepatosplenomegaly and microabscess. These findings might be useful in diagnosis of visceral candidiasis. (author)

  4. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype

    Akagi, Tadayuki; Ogawa, Seishi; Dugas, Martin; KAWAMATA, NORIHIKO; Yamamoto, Go; Nannya, Yasuhito; Sanada, Masashi; Miller, Carl W.; Yung, Amanda; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia; Koeffler, H. Phillip

    2009-01-01

    In this study, single-nucleotide polymorphism microarray analysis was employed to identify hidden genomic abnormalities in patients with acute myeloid leukemia. The findings suggest that at least one half of cases with normal karyotype have readily identifiable genomic abnormalities.

  5. Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

    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.

  6. Stepwise discriminant function analysis for rapid identification of acute promyelocytic leukemia from acute myeloid leukemia with multiparameter flow cytometry.

    Chen, Zhanguo; Li, Yan; Tong, Yongqing; Gao, Qingping; Mao, Xiaolu; Zhang, Wenjing; Xia, Zunen; Fu, Chaohong

    2016-03-01

    Diagnosis of acute promyelocytic leukemia (APL) has been accelerated by multiparameter flow cytometry (MFC). However, diagnostic interpretation of MFC readouts for APL depends on individual experience and knowledge, which inevitably increases the risk of arbitrariness. We appraised the feasibility of using stepwise discriminant function analysis (SDFA) based on MFC to optimize the minimal variables needed to distinguish APL from other acute myeloid leukemia (AML) without complicated data interpretation. Samples from 327 patients with APL (n = 51) and non-APL AML (n = 276) were randomly allocated into training (243 AML) and test sets (84 AML) for SDFA. The discriminant functions from SDFA were examined by correct classification, and the final variables were validated by differential expression. Finally, additional 20 samples from patients with atypical APL and AML confusable with APL were also identified by SDFA method and morphological analysis. The weighed discriminant function reveals seven differentially expressed variables (CD2/CD9/CD11b/CD13/CD34/HLA-DR/CD117), which predict a molecular result for APL characterization with an accuracy that approaches 99 % (99.6 and 98.8 % for AML samples in training and test sets, respectively). Furthermore, the SDFA outperformed either single variable analysis or the more limited 3-component analysis (CD34/CD117/HLA-DR) via separate SDFA, and was also superior to morphological analysis in terms of diagnostic efficacy. The established SDFA based on MFC with seven variables can precisely and rapidly differentiate APL and non-APL AML, which may contribute to the urgent initiation of all-trans-retinoic acid-based APL therapy. PMID:26759321

  7. Treosulfan, Fludarabine Phosphate, and Total Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

    2016-06-20

    Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

  8. Management of acute promyelocytic leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet

    M.A. Sanz (Miguel Angel); D. Grimwade (David); M.S. Tallman (Martin); B. Löwenberg (Bob); P. Fenaux (Pierre); E.H. Estey (Elihu); T. Naoe (Tomoki); E. Lengfelder (Eva); T. Büchner (Thomas); H. Döhner (Hartmut); A.K. Burnett (Alan); F. Lo-Coco (Francesco)

    2009-01-01

    textabstractThe introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with

  9. Myeloid Sarcoma: An Unusual Presentation of Acute Promyelocytic Leukemia Causing Spinal Cord Compression

    Tay Za Kyaw; Jayaranee A.s. Maniam; Ping Chong Bee; Edmund Fui Min Chin; Veera Sekaran Nadarajan; Hemalatha Shanmugam; Khairul Azmi Abd Kadir

    2012-01-01

    Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on t...

  10. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Laura Villarreal-Martínez; José Carlos Jaime-Pérez; Marisol Rodríguez-Martínez; Oscar González-Llano; David Gómez-Almaguer

    2012-01-01

    Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recov...

  11. Translocation (8;21) acute myeloid leukemia presenting as severe aplastic anemia

    Enkhtsetseg Purev; Bogdan Dumitriu; Hourigan, Christopher S.; Young, Neal S.; Townsley, Danielle M.

    2014-01-01

    We report a case of t(8;21) acute myeloid leukemia presenting as severe aplastic anemia. While initial bone marrow biopsy lacked any cytogenetic abnormalities in 20 analyzed metaphases, repeat bone marrow biopsy eight days later demonstrated this translocation. Initial cytogenetic analysis of 20 metaphases was therefore insufficient to make the diagnosis of hypocellular acute myeloid leukemia. We discuss that further complementary molecular tests, such as CGH, would likely provide a more robu...

  12. Acute promyelocytic leukemia in a hemophilia A patient:a case report

    张磊; 李洪强; 赵辉; 王婷婷; 季林祥; 杨仁池; 韩忠朝

    2004-01-01

    @@ Acute promyelocytic leukemia (APL) is the M3 subtype of the French-American-British (FAB) classification of acute myeloid leukemia (AML). Hemophilia is a congenital bleeding disorder characterized by a deficiency of coagulation factor VIII or IX. In our center, more than one thousand patients with haemophilia A have been treated since 1980.1 In June 2002, APL was first diagnosed in one person with haemophilia (PWH). The coincidence of these two diseases led to challenges in developing a treatment strategy.

  13. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin;

    2012-01-01

    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  14. Outcome of Adult Acute Lymphoblastic Leukemia in South East of Iran (Zahedan)

    Mashhadi, Mohammad Ali; Koushyar, Mohhamad Mahdi; Mohammadi, Mehdi

    2012-01-01

    Background Acute lymphoblastic leukemia is a lymphoid malignancy, resulting from autonomous proliferation of monoclonal abnormal stem cell. The aim of this study was to evaluate the response rate and prognostic factor of adult patients suffering from acute lymphoblastic leukemia, who were treated with chemotherapy in south east of Iran and demographic methods were used for this study. Methods This study was conducted in Ali Ebne Abitaleb Hospital in south east of Iran (Zahedan) from 2003-2010...

  15. FLT3 and NPM-1 mutations in a cohort of acute promyelocytic leukemia patients from India

    Suchitra Swaminathan; Swati Garg; Manisha Madkaikar; Maya Gupta; Farah Jijina; Kanjaksha Ghosh

    2014-01-01

    Background: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) and is reported to show better response to anthracyclin based chemotherapy. A favorable overall prognosis over other subtypes of AML has been reported for APL patients but still about 15% patients relapse. Methods: This study evaluated the presence of Famus like tyrosine kinase-3 (FLT3) and nucleophosmin-1 (NPM1) gene mutations in a cohort of 40 APL patients. Bone marrow/pe...

  16. TELOMERASE ACTIVITY AND hTERT mRNA EXPRESSION IN ACUTE LEUKEMIA

    何冬梅; 张洹

    2004-01-01

    Objective: To investigate the clinical implications of telomerase activity and human telomerase reverse transcriptase (hTERT) expression as useful diagnostic marker in acute leukemia. Methods: Expression of hTERT was detected by reverse transcription- polymerase chain reaction (RT-PCR) in 24 cases with acute leukemia and in 12 normal persons. Quantitative levels of telomerase activity were examined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). Results: In the bone marrow and peripheral blood of 24 acute leukemia, telomerase activity was detected in 75% of the samples, with absorbances (A) of 0.538(0.062 and 0.463(0.054, respectively. Whereas in 12 normal peripheral blood, telomerase activity had only a positive rate of 8.3%, with A value of 0.16(0.012. telomerase activities in the bone marrow and peripheral blood of acute leukemia were significantly higher than in normal control (P<0.05). RT-PCR analysis revealed that hTERT mRNA was expressed in 79.17%(19/24) of acute leukemia, but in only 1 of 12 normal peripheral blood. In 24 acute leukemias, 17 cases had both positive telomerse activity and hTERT mRNA expression. The expression of hTERT mRNA is correlated with telomerase activity (P<0.01). Conclusion: Telomerase and hTERT mRNA could be useful in diagnosis of acute leukemia. hTERT gene expression was strongly associated with telomerase activity in acute leukemia.

  17. Osteoporosis resulting from acute lymphoblastic leukemia in a 7-year-old boy: a case report

    Salim, Hendra; Ariawati, Ketut; Suryawan, Wayan Bikin; Arimbawa, Made

    2014-01-01

    Introduction Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Etiological factors responsible for osteoporosis secondary to chronic illness include immobility, pubertal delay and other hormonal disturbances. Rarely, it can be a manifestation of acute lymphoblastic leukemia. Most of the reported bone fracture incidences associated with acute lymphoblastic leukemia occur during the course of the chemotherapy, not...

  18. Association of asthma with the risk of acute leukemia and non-Hodgkin lymphoma

    ZHOU, MIN-HANG; Yang, Qing-Ming

    2015-01-01

    An increasing incidence of hematological malignancies has been observed in children and adults worldwide over the last few decades. Asthma is a common chronic inflammatory disease. The aim of the present meta-analysis was to evaluate the potential association between a history of asthma and the risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL). A literature search was performed through PubMed and the Cochrane Database of Systematic Reviews...

  19. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

  20. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, tho...

  1. Basal ganglia calcification on CT-scanning in children with acute lymphocytic leukemia

    Calcification occurring in the basal ganglia in children with acute hympocytic leukemia following therapy is uncommon and to the best of our knowledge has not been reported prior to therapy. Eleven cases of bilateral symmetrical calcification in the basal ganglia were noted in 2350 CT scans, two being in children with acute lymphocytic leukemia. In one of the two cases, calcification was present prior to therapy. (orig.)

  2. The role of HOX genes in normal hematopoiesis and acute leukemia

    Alharbi, RA; Pettengell, R; Pandha, HS; Morgan, R

    2013-01-01

    The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overex...

  3. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells

    Ding, Husheng; McDonald, Jennifer S.; Yun, Seongseok; Schneider, Paula A.; Peterson, Kevin L.; Flatten, Karen S.; Loegering, David A.; Ann L Oberg; Riska, Shaun M.; Huang, Shengbing; Sinicrope, Frank A.; Adjei, Alex A.; Judith E Karp; Meng, X. Wei; Kaufmann, Scott H.

    2014-01-01

    Although farnesyltransferase inhibitors have shown promising activity in relapsed lymphoma and sporadic activity in acute myelogenous leukemia, their mechanism of cytotoxicity is incompletely understood, making development of predictive biomarkers difficult. In the present study, we examined the action of tipifarnib in human acute myelogenous leukemia cell lines and clinical samples. In contrast to the Ras/MEK/ERK pathway-mediated Bim upregulation that is responsible for tipifarnib-induced ki...

  4. Development of acute leukemia in a known case of fanconi anaemia ( aplastic anaemai

    Preeti Jhaveri

    2013-01-01

    Full Text Available Fanconi anemia is an autosomal recessive disease associated with an abnormal DNA damage. Although Fanconi anemia is well known for its association of Aplastic anemia and characteristic birth defects, leukemia and solid tumors also occur at a high rate in this group of patients. A patient male / 20yrs, known case of Fanconi anemia presented with ulcer over left lower limb. On further evaluation, the patient was found to have pancytopenia and his peripheral smear revealed many atypical blast like cells. So bone marrow study was done which revealed it to be Acute leukemia probably Acute Myeloid leukemia.

  5. Unilateral hypopyon in a child as a first and sole presentation in relapsing acute lymphoblastic leukemia

    Wadhwa Neeraj

    2007-01-01

    Full Text Available Ocular manifestations form a part of the spectrum of varied clinical presentations in leukemias. Most of the ophthalmic manifestations are related to central nervous system leukemia and bone marrow relapse. We report a case of acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL in a pediatric patient. Anterior chamber paracentesis was performed in a four-year-old male child presenting with unilateral treatment-resistant hypopyon after remission of ALL. Examination of aqueous humor aspirate revealed presence of malignant cells. Atypical hypopyon, even unilateral can be an indication of relapsing ALL in a child.

  6. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

    Kensuke Matsumoto; Akira Kitanaka; Makiko Uemura; Fusako Waki; Tetsuya Fukumoto; Hiroaki Ohnishi; Yoshitsugu Kubota; Toshihiko Ishida

    2011-01-01

    Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration,and that hematological adverse events were relatively rare. PPyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-Ⅱ inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.

  7. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Anna Falanga

    2011-12-01

    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  8. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  9. The evolution of clinical trials for infant acute lymphoblastic leukemia

    Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified

  10. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Laura Russo

    2011-01-01

    Full Text Available

    Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC.

    Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes.

    ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field.

    In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  11. Transformation of myelodysplastic syndromes into acute myeloid leukemias

    施均; 邵宗鸿; 刘鸿; 白洁; 曹燕然; 何广胜; 凃梅峰; 王秀丽; 郝玉书; 杨天楹; 杨崇礼

    2004-01-01

    Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83±24.50)%], CD13 [(36.38±33.84)%], monocytic antigen CD14 [(38.50±24.60)%], and stem cell marker CD34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31

  12. Posterior reversible encephalopathy syndrome following acute pancreatitis during chemotherapy for acute monocytic leukemia.

    Nishimoto, Mitsutaka; Koh, Hideo; Bingo, Masato; Yoshida, Masahiro; Nanno, Satoru; Hayashi, Yoshiki; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

    2014-05-01

    We describe an 18-year-old man with acute leukemia who presented with posterior reversible encephalopathy syndrome (PRES) shortly after developing acute pancreatitis. On day 15 after the third consolidation course with high-dose cytarabine, treatment with broad-spectrum antibiotics was initiated for febrile neutropenia. On day 16, he developed septic shock, and subsequently, acute respiratory distress syndrome (ARDS). After adding vancomycin, micafungin and high-dose methylprednisolone (mPSL) to his treatment regimen, these manifestations subsided. On day 22, he received hemodialysis for drug-induced acute renal failure. On day 24, he developed acute pancreatitis possibly due to mPSL; the following day he had generalized seizures, and was intubated. Cerebrospinal fluid findings were normal. Brain MRI revealed hyperintense signals on FLAIR images and increased apparent diffusion coefficient values in the sub-cortical and deep white matter areas of the bilateral temporal and occipital lobes, indicative of vasogenic edema. Thus, we diagnosed PRES. Blood pressure, seizures and volume status were controlled, with MRI findings showing improvement by day 42. He was extubated on day 32 and discharged on day 49 without complications. Although little is known about PRES following acute pancreatitis, clinicians should be aware that this condition may develop. PMID:24881921

  13. Hypergranular precursor B-cell acute lymphoblastic leukemia in a 16-year-old boy

    Tembhare Prashant

    2009-07-01

    Full Text Available Presence of cytoplasmic granules in the blasts is a well known feature of myeloid leukemia. ALL presenting with the numerous cytoplasmic granules in blasts is a rarity and may be misdiagnosed as acute myeloid leukemia. We describe a rare case of hypergranular precursor B-cell acute lymphoblastic leukemia (ALL in an adolescent male expressing CD10, CD19, CytoCD22, CD34, as well as CD13 and CD117. The blasts were cytochemically negative for myeloperoxidase (MPO, and acid phosphatase (ACP but were positive for non-specific esterase (NSE. In centers where immunophenotypic panel is usually decided on the basis of morphology with limited antibodies may result in an erroneous typing of such rare diseases. Hence it is important to be aware of this rare entity and to confirm the lineage of acute leukemia by using a comprehensive panel of antibodies for immunophenotypic analysis.

  14. Primitive neuroectodermal tumor arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. Case report

    We report a case of primitive neuroectodermal tumor (PNET) arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. A 15-year-old boy with a history of acute lymphoblastic leukemia, at the age of 7, underwent chemotherapy and 14 Gy of radiotherapy to the whole brain. He was admitted to our department due to the development of aphasia, right hemiparesis and generalized convulsive seizure. MRI showed an irregularly enhanced mass in the left frontal lobe. A gross total removal of the tumor was performed and histological examination showed it to be PNET. Postoperatively, the patient underwent 20 Gy of radiotherapy to the whole brain and 42 Gy of local radiotherapy. Follow-up MRI showed no evidence of recurrent tumor 4 months after the radiotherapy. This tumor was thought to be a secondary brain tumor arising in this survivor of childhood acute lymphoblastic leukemia and it is a rare complication of successful leukemia treatment. (author)

  15. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Yiju Hou

    2015-02-01

    Full Text Available Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells, we investigated the possible synergistic anti-cancer effects between ginseng extract Rg3 and cytarabine on acute myeloid leukemia cells. Results of this study demonstrate that Rg3 can enhance the anti-proliferation effect of cytarabine on hl60 cells and may decrease the dosage of cytarabine needed for acute myeloid leukemia treatment.

  16. Pictorial essay: Acute neurological complications in children with acute lymphoblastic leukemia

    Seema A Kembhavi

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the commonest childhood malignancy with high cure rates due to recent advances in central nervous system (CNS prophylaxis. The disease per se, as well as the prophylactic therapy, predisposes the child to complications such as cerebrovascular events, infections, drug toxicities, etc. The purpose of this study is to highlight the pathophysiology and the imaging features (with appropriate examples of these complications and to propose a diagnostic algorithm based on MRI. Interpreting these scans in the light of clinical inputs very often helps the radiologist reach an appropriate diagnosis and help treatment and management.

  17. The Relationship between Clinical Feature, Complex Immunophenotype, Chromosome Karyotype, and Outcome of Patients with Acute Myeloid Leukemia in China

    Bingjie Ding; Lanlan Zhou; Xuejie Jiang; Xiaodong Li; Qingxiu Zhong; Zhixiang Wang; Zhengshan Yi; Zhongxin Zheng; Changxin Yin; Rui Cao; Libin Liao; Fanyi Meng

    2015-01-01

    Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly+AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly−AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall s...

  18. Targeted Therapy: The New Lease on Life for Acute Promyelocytic Leukemia, and Beyond%Targeted Therapy: The New Lease on Life for Acute Promyelocytic Leukemia, and Beyond

    2012-01-01

    Under a research project funded by NSFC, Prof. Chen Saijuan of Shanghai Jiaotong University Ruijin Hospital and Prof. Zhou Guangbiao of Institute of Zoology of CAS, published a review article entitled "Targeted therapy. The new lease on life for acute promyelocytic leukemia, and beyond" on IUBMB Life, 64(8). 671-675, 2012

  19. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

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

    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.)

  1. Post-therapeutic acute malignant myeloproliferative syndrome and acute nonlymphocytic leukemia in non-Hodgkin's lymphoma

    In a prospective randomized study of treatment with radiation therapy (RT) or RT + chemotherapy (CT) for patients with non-Hodgkin's lymphoma Stages I-III, one patient developed an acute malignant myeloproliferative syndrome (AMMS) and four others acute nonlymphocytic leukemia (ANLL). There was correlation between the intensity of treatment and development of this complication: Among patients treated with local radiation with or without chemotherapy no cases of AMMS or ANLL were observed. However, patients treated with total lymphoid irradiation alone (TLI) had an observed to expected ratio of 162. Among patients treated with TLI plus CT this ratio increased to over 1000. The cytogenetic, clinical, and hematologic abnormalities of these patients are discussed

  2. Acute Lymphoblastic Leukemia Transformation in Polycythemia Vera: A Rare Phenomenon.

    Gaweł, Władysław B; Helbig, Grzegorz; Boral, Kinga; Kyrcz-Krzemień, Sławomira

    2016-06-01

    Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. She was found to be positive for the JAK2V617F mutation. Patient received an ALL induction regimen and achieved complete remission with negative minimal residual disease by flow cytometry. The post-chemotherapy study for the JAK2V617F mutation was positive. Patient has remained in remission for 4 months. A suitable donor searching was initiated. Post-PV ALL is an extremely rare phenomenon. Due to poor prognosis, an allogeneic stem cell transplantation should be considered in fit patients who achieved remission. PMID:27408357

  3. TREATMENT OF ADOLESCENT AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Josep-Maria Ribera

    2014-07-01

    Full Text Available The primary objective of this review was to update and discuss the current concepts andthe results of the treatment of acute lymphoblastic leukemia (ALL in adolescents and young adults(AYA. After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALLin the AYA population, the main retrospective comparative studies stating the superiority ofpediatric over adult-based protocols were reviewed. The most important prospective studies inyoung adults using pediatric inspired or pediatric unmodified protocols were also reviewedemphasizing their feasibility at least up to the age of 40 yr and their promising results, with eventfreesurvival rates of 60-65% or greater. Results of trials from pediatric groups have shown that theunfavourable prognosis of adolescents is no more adequate. The majority of the older adolescentswith ALL can be cured with risk-adjusted and minimal residual disease-guided intensivechemotherapy, without stem cell transplantation. However, some specific subgroups, which aremore frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like,deserve particular attention. In summary, the advances in treatment of ALL in adolescents havebeen translated to young adults, and that explains the significant improvement in survival of thesepatients in recent years.

  4. Epigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions.

    Kim, Tae Kon; Gore, Steven D; Zeidan, Amer M

    2015-07-01

    Epigenetic modifications affect gene expression without changes in the actual DNA sequence. Two of the most important mechanisms include DNA methylation and histone tail modifications (especially acetylation and methylation). Epigenetic modulation is a part of normal physiologic development; its dysregulation is an important mechanism of pathogenesis of some cancers, including acute myeloid leukemia (AML). Despite significant progress in understanding the pathogenesis of AML, therapeutic options remain quite limited. Technological advances have facilitated understanding of aberrant DNA methylation and histone methylation/acetylation as key elements in the development of AML and uncovered several recurrent mutations in genes important for epigenetic regulation. However, much remains to be learned about how to exploit this knowledge for epigenetic therapeutic targeting. Currently, no epigenetic therapy is approved for the treatment of AML, although two DNA methyltransferase inhibitors (azacitidine and decitabine) are commonly used in clinical practice. Among the other epigenetic modifiers undergoing research in AML, the histone deacetylase inhibitors are the most studied. Other promising drugs, such as inhibitors of histone methylation (eg, EZH2 and DOT1L inhibitors), inhibitors of histone demethylases (eg, LSD1 inhibitors), inhibitors of bromodomain-containing epigenetic "reader" BET proteins, and inhibitors of mutant isocitrate dehydrogenases, are at early stages of clinical evaluation. PMID:26111464

  5. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  6. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

    2016-04-01

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  7. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

  8. MRI of aseptic osteonecrosis in children with acute lymphoblastic leukemia

    Purpose: To evaluate the incidence, localisation, and course of symptomatic aseptic osteonecrosis (AON) in children undergoing treatment for acute lymphoblastic leukemia (ALL). Methods: 72 MRI examinations obtained from 26 children with bone pain selected from a group of 121 children with ALL were evaluated retrospectively. The area of the AON was determined by computer assisted planimetry. Follow-up examinations after 2-5 years were considered. Results: 10/121 (8.3%) of the children had symptomatic AON, the number of lesions varied between 1 and 24 per child. 62/66 lesions were localized within the lower extremities. 58% of the AON were positioned in the epiphysis and 42% in the meta- and diaphysis. The mean area of AON was 7.6 cm2 with a range of 0.5 to 50 cm2. Follow-up examinations revealed a regression in 19 AON, no change in 43 and a progression in 4 lesions. AON within the epiphysis with joint involvement or lesions greater than 9 cm2 more frequently showed a progression of AON with final joint destruction. An elevated risk for AON was seen in children older than 10 years and in children with intensified chemotherapy due to high-risk ALL. Conclusion: AON is a common complication in ALL-children under chemotherapy. Most frequently, the course is benign but large AON with joint involvement have an elevated risk for progression of AON with final joint destruction. (orig.)

  9. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  10. Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia.

    Chen, Yan; Xu, Qian; Ji, Dexiang; Wei, Yanlin; Chen, Huamei; Li, Tingting; Wan, Bolin; Yuan, Liya; Huang, Ruibin; Chen, Guoan

    2016-05-01

    Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment. PMID:26596840

  11. BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy.

    Slone, William L; Moses, Blake S; Hare, Ian; Evans, Rebecca; Piktel, Debbie; Gibson, Laura F

    2016-04-26

    The bone marrow niche has a significant impact on acute lymphoblastic leukemia (ALL) cell phenotype. Of clinical relevance is the frequency with which quiescent leukemic cells, in this niche, survive treatment and contribute to relapse. This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to chemotherapy induced cell death. Combination treatment of caffeine, which increases BCL6 expression in ALL cells, with chemotherapy extended the event free survival of mice. These data suggest that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. PMID:27015556

  12. [Transient hyperphosphatasemia observed in a boy with acute lymphoblastic leukemia].

    Kikuchi, S; Fujikawa, S; Hara, K; Ohira, M; Kojima, C; Maekawa, M

    1997-08-01

    A detailed time course of alkaline phosphatase (ALP; EC3.1.3.1) activity of transient hyperphosphatasemia (TH) in a 9-year-old boy with acute lymphoblastic leukemia (ALL) is described. The patient's serum ALP activity rose transiently to 49 times the upper limit of normal adult, without any evidences of hepatic and bone disease. The half-life of ALP activity was calculated about 10 days. We characterized ALP isoenzymes by usual electrophoresis using cellulose acetate membrane (Titan III iso-vis) and polyacrylamide disc gel (AlkPhor), and isoelectric focusing using polyacrylamide slab gel. The former two methods showed typical two bands (fast-alpha 2 and alpha 2 beta bands) and the latter one method revealed more basic bands of liver and bone, suggesting the extensive sialylation. The patient complained fever and diarrhea. Enterococcus faecium was detected from his stool. Etiologically, two more patients in the same ward showed TH in the same period. It suggested TH would be occurred by infectious states. Awareness of such benign forms of hyperphosphatasemia not related to malignancy will aid the physician in the differential diagnosis of elevated ALP activity. PMID:9283233

  13. Immunophenotypes and Immune Markers Associated with Acute Promyelocytic Leukemia Prognosis

    Fang Xu

    2014-01-01

    Full Text Available CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of acute promyelocytic leukemia (APL. The present study aimed to explore the role of APL immunophenotypes and immune markers as prognostic predictors on clinical outcomes. A total of 132 patients with de novo APL were retrospectively analyzed. Immunophenotypes were determined by flow cytometry. Clinical features, complete remission (CR, relapse, and five-year overall survival (OS rate were assessed and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34− immunophenotype was commonly observed in patients with APL. Positive rates for other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%, 78.4%, and 96.6%, respectively. When compared with patients with CD2− APL, patients with CD2+ APL had a significantly higher incidence of early death (50% versus 15.7%; P=0.016, lower CR rate (50% versus 91.1%; P=0.042, and lower five-year OS rate (41.7% versus 74.2%; P=0.018. White blood cell (WBC count before treatment was found to be the only independent risk factor of early death, CR failure, and five-year mortality rate. Flow cytometric immunophenotype analysis can facilitate prompt APL diagnosis. Multivariate analysis has demonstrated that WBC count before treatment is the only known independent risk factor that predicts prognosis for APL in this study population.

  14. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  15. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    Chromosomal abnormalities are present in bone marrow of approximately 50% of newly diagnostic acute nonlymphatic leukemia (ANLL) patients, but their etiologic significance, if any, is unclear. The frequency of environmental exposures, gathered by questionnaire from patients or relatives, was compared in 127 newly diagnosed ANLL patients with marrow abnormalities (AA) and 109 ANLL patients with cytogenetically normal marrow. These represented 73% of de novo patients treated at M. D. Anderson Hospital between 1976 and 1983. AA patients were more likely than NN patients to: report cytotoxic treatment for prior medical conditions, smoke cigarettes, drink alcoholic beverages, and work at occupations with possible exposure to mutagens. No statistically significant associations between aneuploidy and use of other tobacco, avocational exposure to chemicals or exposure to animals were present. Associations between specific abnormalities and prior cytotoxic therapy (deletion of chromosome 7), smoking (extra chromosome 8, inversion chromosome 16), and occupation at the time of diagnosis (translocation between chromosomes 8 and 21) were noted. No association between occupational exposure to benzene or ionizing radiation and the 6 most common chromosomal abnormalities in ANLL patients were noted, although these agents are known to be leukemogenic. Problems with interpreting the above associations, including the high nonresponse rate, a high proportion of surrogate respondents, and the large number of significance tests that were performed, are discussed. These results are consistent with those from previously reported series, and suggest that tumor-specific markers may be present for some exposures in this disease

  16. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  17. Acute promyelocytic leukemia during pregnancy: a systematic analysis of outcome.

    Verma, Vivek; Giri, Smith; Manandhar, Samyak; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-03-01

    The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p < 0.01) and fetal (p < 0.01) complications. To our knowledge, this is the largest systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making. PMID:26110880

  18. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  19. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  20. Probing Mechanical Properties of Jurkat Cells under the Effect of ART Using Oscillating Optical Tweezers

    2015-01-01

    Acute lymphoid leukemia is a common type of blood cancer and chemotherapy is the initial treatment of choice. Quantifying the effect of a chemotherapeutic drug at the cellular level plays an important role in the process of the treatment. In this study, an oscillating optical tweezer was employed to characterize the frequency-dependent mechanical properties of Jurkat cells exposed to the chemotherapeutic agent, artesunate (ART). A motion equation for a bead bound to a cell was applied to describe the mechanical characteristics of the cell cytoskeleton. By comparing between the modeling results and experimental results from the optical tweezer, the stiffness and viscosity of the Jurkat cells before and after the ART treatment were obtained. The results demonstrate a weak power-law dependency of cell stiffness with frequency. Furthermore, the stiffness and viscosity were increased after the treatment. Therefore, the cytoskeleton cell stiffness as the well as power-law coefficient can provide a useful insight into the chemo-mechanical relationship of drug treated cancer cells and may serve as another tool for evaluating therapeutic performance quantitatively. PMID:25928073

  1. Probing mechanical properties of Jurkat cells under the effect of ART using oscillating optical tweezers.

    Samaneh Khakshour

    Full Text Available Acute lymphoid leukemia is a common type of blood cancer and chemotherapy is the initial treatment of choice. Quantifying the effect of a chemotherapeutic drug at the cellular level plays an important role in the process of the treatment. In this study, an oscillating optical tweezer was employed to characterize the frequency-dependent mechanical properties of Jurkat cells exposed to the chemotherapeutic agent, artesunate (ART. A motion equation for a bead bound to a cell was applied to describe the mechanical characteristics of the cell cytoskeleton. By comparing between the modeling results and experimental results from the optical tweezer, the stiffness and viscosity of the Jurkat cells before and after the ART treatment were obtained. The results demonstrate a weak power-law dependency of cell stiffness with frequency. Furthermore, the stiffness and viscosity were increased after the treatment. Therefore, the cytoskeleton cell stiffness as the well as power-law coefficient can provide a useful insight into the chemo-mechanical relationship of drug treated cancer cells and may serve as another tool for evaluating therapeutic performance quantitatively.

  2. Two pairs of monozygotic twins with concordant acute lymphoblastic leukemia (ALL): case report.

    Li, Xue; Sun, Nianzheng; Huang, Xiaoyang; Ju, Xiuli

    2014-07-01

    The occurrence of leukemia in twins is rare but has a crucial implication in the genetic research of leukemia. This report presents 2 pairs of monozygotic twins with precursor B-cell acute lymphoblastic leukemia. Mixed lineage leukemia (MLL)-AF4 fusion genes were found in the twin sisters. This study is the first to report on infant ALL harboring the 46,XY, -4, +10, -13, del(14)(q24), -15, +2mar[4 cells] complex chromosome abnormality. Our report showed that the unified cytogenetic features in monozygotic twins and MLL-AF4 fusion gene may be necessary but insufficient for the clinical development and prognosis of identical twins with leukemia. PMID:24807006

  3. Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts

    Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

  4. Successful treatment with interferon of chicken pox in children with acute leukemia.

    Kim,Byung Soo

    1984-02-01

    Full Text Available Childhood leukemia, especially acute lymphocytic leukemia, can now be completely cured by a multimodality approach in one out of every two patients. Since prolonged maintenance therapy with anti-cancer agents for three years is required for complete cure, a significant problem during this course of treatment is death due to secondary infection. Those with childhood leukemia receiving anti-cancer chemotherapy who became secondarily injected with chicken pox can now be treated successfully with interferon in the four cases reported here. Chicken pox was cured even while one of them was in relapse. Therefore, it can be said that a bright prospect, namely interferon, is on the horizon in the treatment of secondary viral diseases associated with acute leukemia.

  5. 3,3'-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells.

    Lyndsey E Shorey

    Full Text Available Certain bioactive food components, including indole-3-carbinol (I3C and 3,3'-diindolylmethane (DIM from cruciferous vegetables, have been shown to target cellular pathways regulating carcinogenesis. Previously, our laboratory showed that dietary I3C is an effective transplacental chemopreventive agent in a dibenzo[def,p]chrysene (DBC-dependent model of murine T-cell lymphoblastic lymphoma. The primary objective of the present study was to extend our chemoprevention studies in mice to an analogous human neoplasm in cell culture. Therefore, we tested the hypothesis that I3C or DIM may be chemotherapeutic in human T-cell acute lymphoblastic leukemia (T-ALL cells. Treatment of the T-ALL cell lines CCRF-CEM, CCRF-HSB2, SUP-T1 and Jurkat with DIM in vitro significantly reduced cell proliferation and viability at concentrations 8- to 25-fold lower than the parent compound I3C. DIM (7.5 µM arrested CEM and HSB2 cells at the G(1 phase of the cell cycle and 15 µM DIM significantly increased the percentage of apoptotic cells in all T-ALL lines. In CEM cells, DIM reduced protein expression of cyclin dependent kinases 4 and 6 (CDK4, CDK6 and D-type cyclin 3 (CCND3; DIM also significantly altered expression of eight transcripts related to human apoptosis (BCL2L10, CD40LG, HRK, TNF, TNFRSF1A, TNFRSF25, TNFSF8, TRAF4. Similar anticancer effects of DIM were observed in vivo. Dietary exposure to 100 ppm DIM significantly decreased the rate of growth of human CEM xenografts in immunodeficient SCID mice, reduced final tumor size by 44% and increased the apoptotic index compared to control-fed mice. Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL.

  6. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia.

    Munker, Reinhold; Brazauskas, Ruta; Wang, Hai Lin; de Lima, Marcos; Khoury, Hanna J; Gale, Robert Peter; Maziarz, Richard T; Sandmaier, Brenda M; Weisdorf, Daniel; Saber, Wael

    2016-06-01

    Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival. PMID:26903380

  7. Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results

    Vag, Tibor; Krumbein, Ines; Reichenbach, Juergen R.; Lopatta, Eric; Stenzel, Martin; Kaiser, Werner A.; Mentzel, Hans-Joachim [Friedrich Schiller University Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Kentouche, Karim; Beck, James [Friedrich Schiller University Jena, Department of Pediatrics, Jena (Germany); Renz, Diane M. [Charite University Medicine Berlin, Department of Radiology, Campus Virchow Clinic, Berlin (Germany)

    2011-08-15

    Routine assessment of body iron load in patients with acute leukemia is usually done by serum ferritin (SF) assay; however, its sensitivity is impaired by different conditions including inflammation and malignancy. To estimate, using MRI, the extent of liver iron overload in children with acute leukemia and receiving blood transfusions, and to examine the association between the degree of hepatic iron overload and clinical parameters including SF and the transfusion iron load (TIL). A total of 25 MRI measurements of the liver were performed in 15 children with acute leukemia (mean age 9.75 years) using gradient-echo sequences. Signal intensity ratios between the liver and the vertebral muscle (L/M ratio) were calculated and compared with SF-levels. TIL was estimated from the cumulative blood volume received, assuming an amount of 200 mg iron per transfused red blood cell unit. Statistical analysis revealed good correlation between the L/M SI ratio and TIL (r = -0.67, P = 0.002, 95% confidence interval CI = -0.83 to -0.34) in patients with acute leukemia as well as between L/M SI ratio and SF (r = -0.76, P = 0.0003, 95% CI = -0.89 to -0.52). SF may reliably reflect liver iron stores as a routine marker in patients suffering from acute leukemia. (orig.)

  8. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1) GeneExpression in Egyptian Patients with AcuteMyeloid Leukemia

    Nadia El Menshawy; Doaa Shahin; Hayam Fathi Ghazi

    2014-01-01

    Objective: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1) gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic sig...

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

    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

  10. IGFBP7 induces apoptosis of acute myeloid leukemia cells and synergizes with chemotherapy in suppression of leukemia cell survival

    Verhagen, H JMP; de Leeuw, D C; Roemer, M GM; Denkers, F; Pouwels, W; Rutten, A; Celie, P H; Ossenkoppele, G. J.; Schuurhuis, G. J.; Smit, L.

    2014-01-01

    Despite high remission rates after chemotherapy, only 30–40% of acute myeloid leukemia (AML) patients survive 5 years after diagnosis. This extremely poor prognosis of AML is mainly caused by treatment failure due to chemotherapy resistance. Chemotherapy resistance can be caused by various features including activation of alternative signaling pathways, evasion of cell death or activation of receptor tyrosine kinases such as the insulin growth factor-1 receptor (IGF-1R). Here we have studied ...

  11. Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene

    Wang, Lingbo; Cai, Weili; Zhang, Wei; Chen, Xueying; Dong, Wenqian; Tang, Dongqi; Zhang, Yun; Ji, Chunyan; Zhang, Mingxiang

    2015-01-01

    An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by acting on different molecular pathways. PARP-1 inhibitors can be used with radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated in AML patients. PARP-1 ...

  12. Molecular mechanisms in differentiation-induction in acute promyelocytic leukemia

    Nigten, Jeannet

    2007-01-01

    Leukemia is a hematological malignancy that is characterized by the clonal expansion of immature hematopoietic cells, which have escaped from the tightly coordinated cell cycle regulation, differentiation and apoptosis controls. In general, leukemia is characterized by a variety of mutations in path

  13. Unraveling Glucocorticoid Resistance In MLLrearranged Infant Acute Lymphoblastic Leukemia

    J.A.P. Hagelstein (Jill)

    2014-01-01

    markdownabstract__Abstract__ In the Netherlands, approximately 650 children aged between 0 and 18 years are diagnosed with cancer every year, including ~120 patients suffering from leukemia. Leukemia (Greek for leukos - white, and haima for blood) is a type of cancer characterized by an abnormal in

  14. Filariasis in an infant with B-cell acute lymphoblastic leukemia: a rare enigma

    Yadav, Yogesh Kumar; Sipayya, Varuna; KHANNA, Geetika; Gupta, Oneal

    2011-01-01

    Filariasis, a tropical parasitic infection, is a common public health problem in the Indian sub-continent. Occurrence of filariasis with acute lymphoblastic leukemia (ALL) is unusual, particularly in infants, since filariasis has a long incubation period of about 1 year. Though, there are case reports of leishmaniasis, malaria and other vector borne diseases seen in association with leukemias, filariasis co-existing with ALL has not been documented to the best of our knowledge. We report an i...

  15. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI

    Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family. (orig.)

  16. Phosphoproteomic profiling analysis in pediatric acute leukemias and in solid tumors of the adult

    We analyzed 120 pediatric patients affected with B-cell AL (B-Acute Lymphoblastic Leukemia) by Reverse Phase Protein Arrays (RPPA). Leukemia cells from bone marrow aspirates were stored in liquid nitrogen in the Bio Bank of the Laboratory of Pediatric Onco hematology in Padova. Clinical data, such as immuno phenotype, outcome, response to therapy and chromosomal translocations, were collected for all the patients

  17. THE IMPORTANCE TO RECOGNIZE ORAL MANIFESTATIONS OF ACUTE LEUKEMIA (CASE REPORT)

    Anandina Irmagita; Siti Aliyah Pradono

    2015-01-01

    Dentists could be the first health providers who detect the oral manifestation of early symptoms of leukemia. The management of three cases of acute leukemia, which had intra oral manifestations that were unnoticed by the dentists, are discussed. Before being referred to the Oral Medicine Department, these patients had undergone invasive dental treatment by their dentist, which had caused complication such as bleeding. After being referred, the patients had undergone non-invasive dental exami...

  18. Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects

    Jansson, Johan; Hsu, Yu-Chiao; Kuzin, Igor I.; Campbell, Andrew; Mullen, Craig A.

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation is often performed for patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are generally weak and the mechanisms of this weakness are unknown. These studies tested the hypothesis that ALL cells that have survived conventional chemotherapy in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice were injected with mur...

  19. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Yiju Hou; Xiaodong Liu; Zhonghai Yuan; Yan Li

    2015-01-01

    Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells...

  20. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    Schotte, Diana; Menezes, Renee; Akbari Moqadam, Farhad; Khankahdani, Leila Mohammadi; Lange-Turenhout, Ellen; Chen, Caifu; Pieters, Rob; de Boer, Monique

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression levels of 397 microRNA (including novel microRNA) were measured by quantitative real-time polymerase chain reaction in 81 cases of pediatric leukemia and 17 normal hematopoietic control cases. Res...

  1. Residential Proximity to Agricultural Pesticide Applications and Childhood Acute Lymphoblastic Leukemia

    Rull, Rudolph P.; Gunier, Robert; Von Behren, Julie; Hertz, Andrew; Crouse, Vonda; Buffler, Patricia A.; Reynolds, Peggy

    2009-01-01

    Ambient exposure from residential proximity to applications of agricultural pesticides may contribute to the risk of childhood acute lymphoblastic leukemia (ALL). Using residential histories collected from the families of 213 ALL cases and 268 matched controls enrolled in the Northern California Childhood Leukemia Study, the authors assessed residential proximity within a half-mile (804.5 meters) of pesticide applications by linking address histories with reports of agricultural pesticide use...

  2. Glucocorticoid use in acute lymphoblastic leukemia: comparison of prednisone and dexamethasone

    Inaba, Hiroto; Pui, Ching-Hon

    2010-01-01

    Glucocorticoids (prednisone and dexamethasone) play an essential role in the treatment of acute lymphoblastic leukemia (ALL) but their optimal doses and bioequivalence have not been established. Pre-clinical studies showed that dexamethasone has a longer half-life and better central nervous system (CNS) penetration. In prospective randomized trials, dexamethasone yielded better control of CNS leukemia. At a prednisone (mg)/dexamethasone (mg) dose ratio less than 7, dexamethasone treatment (6–...

  3. Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphocytic leukemia

    Cases of radiation-induced glioma in humans are extremely rare. A 2-year-old boy with acute lymphocytic leukemia had received prophylactic cranial irradiation (2400 rad/2 1/2 weeks) and intrathecal methotrexate. Five years later he developed a glioblastoma multiforme on the left cerebral hemisphere while the leukemia was in remission. This is the first reported association of these disorders. It is possible that the glioma may have been induced by radiation and/or chemotherapy

  4. The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias

    Riccardo Masetti; Salvatore Serravalle; Carlotta Biagi; Andrea Pession

    2011-01-01

    Acute leukemia is the most common type of childhood and adolescence cancer, characterized by clonal proliferation of variably differentiated myeloid or lymphoid precursors. Recent insights into the molecular pathogenesis of leukemia have shown that epigenetic modifications, such as deacetylation of histones and DNA methylation, play crucial roles in leukemogenesis, by transcriptional silencing of critical genes. Histone deacetylases (HDACs) are potential targets in the treatment of leukaemia,...

  5. Transient Appearance of Blasts in Peripheral Smear in Paediatric Patient with Acute Aleukemic Leukemia

    Vaghasiya Viren L; Parikh Hina S; Patel Divyesh V; Taviad Dilip S

    2012-01-01

    Acute leukemia can present as leukemic blast in peripheral blood & bone marrow or in some cases in only in bone marrow. Here we present unique case of paediatric acute leukaemia which shows blast cells in peripheral blood transiently and without any definitive treatment blast cell disappear from peripheral blood. So diagnosis made previously was questioned, but later on when bone marrow examination was performed it turn out to be acute leukaemia. We haven’t found any reference o...

  6. Association of CYP3A5FNx013 polymorphism with development of acute leukemia

    D Nageswara Rao

    2011-01-01

    Full Text Available Background : CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5FNx013. We investigated the association between CYP3A5FNx013 polymorphism and acute leukemia. Materials and Methods : Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL, 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5FNx013 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0 to detect the association between CYP3A5FNx013 polymorphism and acute leukemia. Results : The CYP3A5FNx013 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ2 - 133.53; df-2, P 0.000. When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL. Conclusion : The results suggest that the CYP3A5FNx013 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.

  7. Serological analysis of cell surface antigens of null cell acute lymphocytic leukemia by mouse monoclonal antibodies.

    Ueda, R; Tanimoto, M; Takahashi, T.; Ogata, S; Nishida, K; Namikawa, R.; Nishizuka, Y; Ota, K.

    1982-01-01

    Nine antigens systems were defined. Two were related to HLA-A,B,C and to Ia-like antigens; the others could be grouped into three categories. (i) NL-22, NL-1: NL-22 antibody reacted with leukemia cells from 12 to 16 cases of null cell acute lymphocytic leukemia (null-ALL) but not with any other type of leukemia tested or with lymphoid cells of various origins. Among cultured cell lines tested, one (NALM-6) of three null-ALL cell lines was positive, the others were negative. Absorption analysi...

  8. Alterations of Lymphoid Enhancer Factor-1 Isoform Expression in Solid Tumors and Acute Leukemias

    Wenbing WANG; Carsten M(U)LLER-TIDOW; Ping JI; Bj(o)rn STEFFEN; Ralf METZGER; Paul M. SCHNEIDER; Hartmut HALFTER; Mark SCHRADER; Wolfgang E. BERDEL; Hubert SERVE

    2005-01-01

    Two major transcripts of lymphoid enhancer factor-1 (LEF-1) have been described. The long isoform with β-catenin binding domain functions as a transcriptional enhancer factor. The short isoform derives from an intronic promoter and exhibits dominant negative activity. Recently, alterations of LEF- 1isoforms distribution have been described in colon cancer. In the current study we employed a quantitative real-time reverse transcription PCR method (TaqMan) to analyze expression of LEF-1 isoforms in a large cohort of human tumor (n=304) and tumor-free control samples (n=56). The highest expression level of LEF-1 was found in carcinoma samples whereas brain cancer samples expressed little. Expression of LEF1 was different in distinct cancer types. For example, the mRNA level of LEF-1 was lower in testicular tumor samples compared with tumor-free control samples. Besides epithelial cancers, significant LEF-1expression was also found in hematopoietic cells. In hematological malignancies, overall LEF-1 level was higher in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis. However,acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of the oncogenic LEF-1 compared with chronic lymphocytic leukemia and chronic myeloid leukemia. Taken together,these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia.

  9. FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

    The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6

  10. Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells.

    Wu, Ching-Fen; Klauck, Sabine M; Efferth, Thomas

    2016-09-01

    Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFκB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFκB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-β and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFκB, which orchestrates all these mechanisms. PMID

  11. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

    Maury, Sébastien; Chevret, Sylvie; Thomas, Xavier; Heim, Dominik; Leguay, Thibaut; Huguet, Françoise; Chevallier, Patrice; Hunault, Mathilde; Boissel, Nicolas; Escoffre-Barbe, Martine; Hess, Urs; Vey, Norbert; Pignon, Jean-Michel; Braun, Thorsten; Marolleau, Jean-Pierre; Cahn, Jean-Yves; Chalandon, Yves; Lhéritier, Véronique; Beldjord, Kheira; Béné, Marie C; Ifrah, Norbert; Dombret, Hervé

    2016-09-15

    Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. Results From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Conclusions Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .). PMID:27626518

  12. Acute lymphoblastic leukemia: Are Egyptian children adherent to maintenance therapy?

    Elhamy Rifky Abdel Khalek

    2015-01-01

    Full Text Available Background, Aims, Settings and Design: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL. A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. Materials and Methods: The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening. Evaluation was done through specific questionnaires for the patients as well as serum 6-MP measurements. Results: Nonadherence was detected in around 56% by questionnaires and around 50% by serum 6-MP level measurement. There was a highly significant correlation between nonadherence as found by the questionnaire and 6-MP level (P - 0.001. Nonadherence was significantly associated with low socioeconomic standard, noneducation and low educational level and large family size by both methods. High cost to come for follow-up visits was significant by questionnaire but not by 6-MP measurement. Adolescent age, the higher number of siblings, lack of written instructions, long time spent per visit, were all associated with higher rates of nonadherence, although none reached statistical significance. Conclusions: Nonadherence is a real problem in pediatric patients. Specific questionnaires can be an excellent reliable method for the routine follow-up of these children, and drug level assay can be requested only for confirmation. This protocol is especially effective in developing countries where financial resources may be limited. Every effort should be made to uncover its true incidence, contributing factors, and best methods of intervention.

  13. Genomic alterations in radiation-induced murine acute myeloid leukemias

    High-dose radiation induces acute myeloid leukemia (AML) in C3H mice, most of which have a high frequent hemizygous deletion around the D2Mit15 marker on the interstitially deleted region of chromosome 2. This region involves PU.1 (Sfpi-1), which is a critical candidate gene for initiation of mouse leukemogenesis. To identify other genes contributing to leukemogenesis with PU.1, we analyzed chromosomal aberrations and changes of expression in 18 AML-related genes in 39 AMLs. Array CGH analysis revealed that 35 out of 39 AMLs had hemizygous deletions of chromosome 2, and recurrent aberrations on chromosomes 4, 6, 8, 10, 11, 12, 15, and 18. Expressions of 18 AML-related genes, within the altered chromosome regions detected by array CGH were analyzed by using RT-PCR and/or real-time PCR. Although Wnt5b, Wnt16, G-CSFR, M-CSFR, SCL/Tal-1 and GATA1 genes were down-regulated, the c-myc gene was, on the contrary, up-regulated. Expression levels of two genes, Rasgrp1 and Wt1, within the deleted region of chromosome 2 correlated with the loss of one of two alleles, although the expression of PU.1 showed an inverse correlation. In addition, the expression level of PU.1 appeared to be higher with a coincidental missense point mutation in DNA-binding domain of PU.1 in the remaining allele, suggesting a feedback transcription control on PU.1. Such an autoregulation might be relevant to the fact that PU.1 haploinsufficiency per se triggers radiation-induced AML. Together with the detection of chromosomal aberrations, these findings provide useful clues to identify cooperative genes that are responsible for molecular pathogenesis of AMLs induced by low-dose-rate radiation exposure. (author)

  14. Base excision repair deficiency in acute myeloid leukemia

    Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system arising from a transformed myeloid progenitor cell. Genomic instability is the hallmark of AML and characterized by a variety of cytogenetic and molecular abnormalities. Whereas 10% to 20% of AML cases reflect long-term sequelae of cytotoxic therapies for a primary disorder, the etiology for the majority of AMLs remains unknown. The integrity of DNA is under continuous attack from a variety of exogenous and endogenous DNA damaging agents. The majority of DNA damage is caused by constantly generated reactive oxygen species (ROS) resulting from metabolic by-products. Base excision repair (BER) is the major DNA repair mechanism dealing with DNA base lesions that are induced by oxidative stress or alkylation. In this study we investigated the BER in AML. Primary AML patients samples as well as AML cell lines were treated with hydrogen peroxide (H2O2). DNA damage induction and repair was monitored by the alkaline comet assay. In 15/30 leukemic samples from patients with therapy-related AML, in 13/35 with de novo AML and 14/26 with AML following a myelodysplastic syndrome, significantly reduced single strand breaks (SSBs) representing BER intermediates were found. In contrast, normal SSB formation was seen in mononuclear cells of 30 healthy individuals and 30/31 purified hematopoietic stem- and progenitor cell preparations obtained from umbilical cord blood. Additionally, in 5/10 analyzed AML cell lines, no SSBs were formed upon H2O2 treatment, either. Differences in intracellular ROS concentrations or apoptosis could be excluded as reason for this phenomenon. A significantly diminished cleavage capacity for 7,8-dihydro-8-oxoguanine as well as for Furan was observed in cell lines that exhibited no SSB formation. These data demonstrate for the first time that initial steps of BER are impaired in a proportion of AML cell lines and leukemic cells from patients with different forms of AML

  15. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  16. Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

    Juliana Godoy Assumpcao

    2013-01-01

    Full Text Available OBJECTIVE To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%. For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%, then TCRG (61.4%, and TCRD and IgK (47.7%; for T-acute lymphocytic leukemia, TCRG (80.0%, and TCRD and Sil-Tal deletion (20.0% were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7. CONCLUSION Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

  17. Diagnostic value of CD117 in differential diagnosis of acute leukemias.

    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 < 0.001). The calculated sensitivity for myeloid involvement was 83, 76, 64, and 41 % for CD13, CD117, CD33, and CD15, respectively (p < 0.001). We concluded that CD117 expression is a specific and rather sensitive marker for differential diagnosis between AML and ALL, and except for M5 subtypes, it fails to determine FAB subtypes; lack of expression in M5 can identify M5b. Therefore, it should be included in the routine primary panel for diagnosis of acute leukemias. PMID:24722823

  18. IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells

    Chen, Xiaoli; Zheng, Junke; Zou, Yizhou; Song, Chun; Hu, Xuemei; Zhang, Cheng Cheng

    2013-01-01

    Background The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs). Methods and results Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. Results IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibiti...

  19. Establishment and genetic characterization of a novel mixed-phenotype acute leukemia cell line with EP300-ZNF384 fusion

    Ping, Nana; Qiu, Huiying; Wang, Qian; Dai, Haiping; Ruan, Changgeng; Ehrentraut, Stefan; Drexler, Hans G.; MacLeod, Roderick A. F.; Chen, Suning

    2015-01-01

    Herein, we describe the establishment and characterization of the first mixed-phenotype acute leukemia cell line (JIH-5). The JIH-5 cell line was established from leukemia cells with B lymphoid/myeloid phenotype from a female mixed-phenotype acute leukemia patient. JIH-5 cells exhibit an immunophenotype comprised of myeloid and B lymphoid antigens. Whole-exome sequencing revealed somatic mutations in nine genes in JIH-5 cells. Transcriptional sequencing of JIH-5 cells identified EP300-ZNF384 ...

  20. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  1. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  2. Down syndrome with microgranular variant of acute promyelocytic leukemia in a child: a case report

    Jain Deepali

    2007-11-01

    Full Text Available Abstract Background Acute promyelocytic leukemia (APL accounts for less than 10% of pediatric AML. Cases of APL in Down syndrome (DS have been described in the literature rarely and it is rarer still to find the microgranular variant (M3v of APL in trisomy 21 patients. Case presentation We present a case of a five-year-old female with Down syndrome diagnosed with acute promyelocytic leukemia (APL. She came to our hospital with bleeding manifestations. Blood and bone marrow examination revealed promyelocytes showing a few fine granules and occasional Auer rods. Based on this morphology and cytochemistry, a diagnosis of APL microgranular variant (M3v was made. Conclusion This case report emphasizes the importance of a high index of suspicion in the diagnosis of acute promyelocytic leukemia microgranular variant in Down syndrome.

  3. Duplication and loss of chromosome 21 in two children with Down syndrome and acute leukemia

    Rogan, P.K.; Close, P.; Gannutz, L. [Pennsylvania State Univ., Hershey, PA (United States)] [and others

    1995-11-06

    Acute leukemia in Down syndrome (DS) is often associated with additional changes in the number of structure of chromosome 21. We present two DS patients whose leukemic karyotypes were associated with changes in chromosome 21 ploidy. Patient 1 developed acute lymphocytic leukemia (type L1); disomy for chromosome 21 was evident in all blast cells examined. Loss of the paternal chromosome in the leukemic clone produced maternal uniparental disomy with isodisomy over a 25-cM interval. The second patient had acute monoblastic leukemia (type M5) with tetrasomy 21 in all leukemic cells. DNA polymorphism analysis showed duplicate paternal chromosomes in the constitutional genotype. The maternal chromosome was subsequently duplicated in the leukemic clone. The distinct inheritance patterns of chromosome 21 in the blast cells of these patients would appear to indicate that leukemogenesis occurred by different genetic mechanisms in each individual. 57 refs., 2 figs., 3 tabs.

  4. Prognosis and complications of acute childhood leukemia after prophylactic treatment of the central nervous

    From 1970 through 1979, 22 children with acute childhood leukemia and in remimmion were treated with preventive central nervous system (CNS) irradiation and simultaneous intrathecal methotrexate. A minimum follow-up duration was five months. Of 22 cases, 20 were acute lymphocytic leukemia (ALL) and 2 were acute myelocytic leukemia (ALL). Five-year cumulative survival rate and five-year relapse free survival rate of ALL case were 48% and 46% respectively. Nor neurological disorders after the prophylactic combined therapy were recognized clinically by the time when this follow-up was finished. Of 15 children with ALL who were followed by computed tomography of the brain, 5(33%) had abnormal findings. Dilatation of the ventricles were seen in 3 cases, and low density areas of the occipital regions in 2 cases. (author)

  5. Infectious events prior to chemotherapy initiation in children with acute myeloid leukemia.

    Carol Portwine

    Full Text Available BACKGROUND: The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia. METHODS: We conducted a retrospective, population-based cohort study that included children and adolescents with acute myeloid leukemia diagnosed and treated at 15 Canadian centers. We evaluated infections that occurred between presentation to the healthcare system (for symptoms that led to the diagnosis of acute myeloid leukemia until initiation of chemotherapy. RESULTS: Among 328 children, 92 (28.0% were neutropenic at presentation. Eleven (3.4% had sterile-site microbiologically documented infection and four had bacteremia (only one Gram negative. Infection rate was not influenced by neutropenia. No child died from an infectious cause prior to chemotherapy initiation. CONCLUSION: It may be reasonable to withhold empiric antibiotics in febrile non-neutropenic children with newly diagnosed acute myeloid leukemia until initiation of chemotherapy as long as they appear well without a clinical focus of infection. Future work could examine biomarkers or a clinical score to identify children presenting with leukemia and fever who are more likely to have an invasive infection.

  6. Hypereosinophilia in Acute Lymphoblastic Leukemia: Two Cases with Review of Literature.

    Sahu, Kamal Kant; Malhotra, Pankaj; Khadwal, Alka; Sachdeva, Manupdesh Singh; Sharma, Prashant; Varma, Neelam; Varma, Subhash Chander

    2015-12-01

    Eosinophilia is rare in acute leukemia at presentation. Discrete reports and case studies in recent years have created significant interest in the field of "Acute leukemia with eosinophilia". We herein present two cases of eosinophilia in association with acute lymphoblastic leukemia with brief review of literature in this field. First case is about 21-year-old female who presented with mediastinal mass along with leukocytosis and hypereosinophilia. On evaluation, she was found to have T cell acute lymphoblastic leukemia. After ruling out benign causes of eosinophilia, she was treated with modified BFM-90 protocol. Her eosinophilia resolved after 4 weeks of induction therapy. Second case is about 32-year-old male who was diagnosed as a case of mixed phenotype leukemia (B cell/myeloid type) along with severe eosinophilia. His hypereosinophilia finally resolved by week 16 of modified BFM-90 protocol. Diagnosing ALL is challenging when eosinophilia is the initial presentation. These two cases emphasize on the importance of considering ALL amongst one of the etiological causes of eosinophilia as delay in diagnosis endangers patient's life at risk. Also eosinophilia per se is an independent poor risk factor, hence prompt diagnosis and early treatment is the key in all such cases. PMID:26306071

  7. [Comparison of protein expression profiles between bortezomib-resistant JurkatB cells with PSMB5 mutation and their parent cells].

    Lü, Shu-Qing; Yang, Jian-Min; Huang, Chong-Mei; Xu, Xiao-Qian; Zhou, Hong; Song, Ning-Xia; Wang, Jian-Min

    2011-08-01

    This study was purposed to investigate the differences of cyto biological characteristics and protein expression levels between bortezomib-resistant T-lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and chemotherapeutic drugs to JurkatB5 cells (end selection concentration of bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and Jurkat cells were analyzed. The cell growth curves were drawn with viable cell counts by trypan blue assay, the colony formation rate were assayed by soft-agar colony culture, and the cell distributions in cell cycle were analyzed by flow cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP and MRP were measured by real-time fluorescence quantitative RT-PCR, the differences of protein expression levels were detected by SpringBio antibody microarray containing 720 proteins. The results showed that the drug resistance multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and JurkatB8 cells did not display significant cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no significant differences in the cell growth curve, colony formation rate and cell distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p > 0.05). There were no significant differences of mRNA expression levels of MDR1, LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable expression points detected by antibody microarray. Among them, 252 protein expression levels were not significantly different between JurkatB5, JurkatB8 and Jurkat cells (II, matrix metalloproteinase-2, tenascin, Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic acid receptor β, integrin β-1), but no proteins were detected

  8. Tonsillitis with acute myeloid leukemia: a case series for caution.

    Thakur, Jagdeep S; Mohindroo, N K; Sharma, D R; Mohindroo, Shobha; Thakur, Anamika

    2013-01-01

    Worldwide, tonsillitis is very common. The most common etiology is cross-infection with bacteria and viruses. These cases are managed with antibiotics and anti-inflammatory drugs without any further investigation because the diagnosis is based on simple clinical examination. Usually, leukemia presents with bleeding, weight loss, lymphadenopathy, fever, and frequent infection. Tonsillitis is a rare first presentation of leukemia. We present 3 cases in which the diagnosis of leukemia was made on routine examination, and in 1 case diagnosis was suspected during tonsillectomy. PMID:23599112

  9. Leukemia

    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. ...

  10. CRIF1 interacting with CDK2 regulates bone marrow microenvironment-induced G0/G1 arrest of leukemia cells.

    Qian Ran

    Full Text Available BACKGROUND: To assess the level of CR6-interacting factor 1 (CRIF1, a cell cycle negative regulator, in patients with leukemia and investigate the role of CRIF1 in regulating leukemia cell cycle. METHODS: We compared the CRIF1 level in bone marrow (BM samples from healthy and acute myeloid leukemia (AML, iron deficiency anemia (IDA and AML-complete remission (AML-CR subjects. We also manipulated CRIF1 level in the Jurkat cells using lentivirus-mediated overexpression or siRNA-mediated depletion. Co-culture with the BM stromal cells (BMSCs was used to induce leukemia cell cycle arrest and mimic the BM microenvironment. RESULTS: We found significant decreases of CRIF1 mRNA and protein in the AML group. CRIF1 overexpression increased the proportion of Jurkat cells arrested in G0/G1, while depletion of endogenous CRIF1 decreased cell cycle arrest. Depletion of CRIF1 reversed BMSCs induced cell cycle arrest in leukemia cells. Co-immunoprecipitation showed a specific binding of CDK2 to CRIF1 in Jurkat cells during cell cycle arrest. Co-localization of two proteins in both nucleus and cytoplasm was also observed with immunofluorescent staining. CONCLUSION: CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor.

  11. The role of radiation therapy in childhood acute leukemia. A review from the viewpoint of basic and clinical radiation oncology

    Radiation therapy has been playing important roles in the treatment of childhood acute leukemia since the 1970s. The first is the preventive cranial irradiation for central nervous system therapy in acute lymphoblastic leukemia. The second is the total body irradiation as conditioning before bone marrow transplantation for children with acute myeloid leukemia in first remission and with acute lymphoblastic leukemia in second remission. Although some late effects have been reported, a part of them could be overcome by technical improvement in radiation and salvage therapy. Radiation therapy for children might have a successful outcome on a delicate balance between efficiencies and potential late toxicities. The role of radiation therapy for childhood acute leukemia was reviewed from the standpoint of basic and clinical radiation oncology in this paper. (author)

  12. Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: The Cancer and Leukemia Group B experience

    Mrózek, Krzysztof; Carroll, Andrew J.; Maharry, Kati; Rao, Kathleen W.; Patil, Shivanand R.; Pettenati, Mark J.; Watson, Michael S.; Arthur, Diane C.; Tantravahi, Ramana; Heerema, Nyla A.; Koduru, Prasad R. K.; Block, AnneMarie W; Qumsiyeh, Mazin B.; Edwards, Colin G.; Sterling, Lisa J.

    2008-01-01

    The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e. adequate) cases, the proportion o...

  13. A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

    Jin, Sun Mi; Jang, Moon Ju; Huh, Ji Young; Park, Myoung Hee; Song, Eun Young; Oh, Doyeun

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patient...

  14. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders;

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings.......More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  15. LEUKEMIC PLEURAL EFF USION AS INITIAL MAN IFESTATION OF ACUTE MYELOID LEUKEMIA: A RARE CASE REPORT

    Rajeev Kumar

    2015-06-01

    Full Text Available Leukemic effusion is an uncommon presentation of Acute Myeloid leukemia with only isolated reports in literature. We report a case of 45 years old female who presented with unilateral pleural effusion and was diagnosed with haematological malignancy on pleural fluid cytology which revealed presence of myeloblasts. Subsequent, peripheral blood smear and bone marrow examination confirmed the diagnosis of Acute Myeloid Leukemia (AML M1. This case report highlights the uncommon presentation of AML as well as utility of meticulous examination of effusion fluids for diagnosing unsuspected malignancies.

  16. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    Yonal Ipek; Dogru Hulya; Aktan Melih

    2012-01-01

    Acute promyelocytic leukemia (APL) is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa) locus on chromosome 17, the great majority of which is t(15; 17)(q24.1; q21.1) (Collins (1998), Melnick and Licht (1999), and Grimwade (1999)). Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA) is a sub...

  17. GENE EXPRESSION OF NOVEL RETROVIRUS ASSOCIATED WITH HUMAN ACUTE MULOID LEUKEMIA

    许晓华; 徐荣臻; 王世炯; 郑树; 朱宁希; 周旋

    2003-01-01

    Objective: To explore the potentiality of retroviral etiology in human acute myeloid leukemia(AML). Methods: The expression of clone 6#11 in leukemic cell samples from 19 AML cases and peripheral blood mononuclear cells (PBMNCs) from 20 controls was studied by means of Northern blot and reversal transcription polymerase chain reaction (RT-PCR). Results: Northern blot and RT-PCR analyses showed that the expression level of clone 6#11 was significantly higher in AML patients than that in control. Conclusion: Northern blot and RT-PCR analyses revealed that the expression of novel retrovirus were associated with acute myeloid leukemia.

  18. Novel targeted therapy for acute myeloid leukemia with a dual FLT3 and JAK2 inhibitor

    Yin-jun LOU

    2012-01-01

    Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor.The use of all-trans retinoic acid (ATRA) and arsenic trioxide,which began from China,has resulted in revolution of the acute promyelocytic leukemia (APL) that appears curable in more than 70% of patients[1].However,the treatment regimen for nonAPL AML particularly in older patients has progressed little in the past two decades.Intensive efforts have been made toward the development of novel target agents,which are based on newfound pathophysiological events crucial for cancers.

  19. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam;

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailabil......Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

  20. Hemiparesis in an Adolescent With Acute Lymphoblastic Leukemia: Everything Is Not Always What it Seems.

    Andina, David; Lassaletta, Alvaro; Sevilla, Julian; Gutierrez, Silvia; Madero, Luis

    2016-01-01

    Acute lymphoblastic leukemia is a common malignancy in childhood. Managing adverse events during treatment can result in very complex situations. A previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia developed on day +55 of induction chemotherapy hemiparesis, dysesthesia, and facial palsy. Blood tests and brain imaging techniques were unremarkable. The patient was diagnosed with a conversion disorder, which completely resolved. Although rare in clinical practice, children and adolescents with cancer do not always have organic pathology explaining their symptoms. Psychiatric disorders such as those of the somatoform spectrum must be considered, particularly in patients with anxiety or depression. PMID:25072371

  1. Acute Myelogenous Leukemia without Maturation with a Retinoic Alpha-Receptor Deletion: A Case Report

    Christopher Trosclair

    2014-06-01

    Full Text Available Acute promyelocytic leukemia (APL is characterized by a t(15;17 which fuses the 17q retinoic acid alpha-receptor sequence to the 15q PML gene sequence. The resulting fusion product plays a role in the development and maintenance of APL, and is very rarely found in other acute myeloid leukemia (AML subtypes. Rare complex APL genomic rearrangements have retinoic acid alpha-receptor sequence deletions. Here we report a retinoic acid alpha-receptor sequence deletion in a case of AML without differentiation. To our knowledge, this is the first example of a retinoic acid alpha-receptor sequence deletion in this AML subtype.

  2. Clinical and microbiological characteristics of perianal infections in adult patients with acute leukemia.

    Chien-Yuan Chen

    Full Text Available BACKGROUND: Perianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed. METHOD: The medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed. RESULT: The prevalence of perianal infection was 6.7% (74 of 1102 in adult patients with acute leukemia. Twenty-three (31% of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028. More than half (n = 61, 53% of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%, anaerobes (n = 18, 15% and Candida (n = 1, 1% from pus culture. Eighteen patients experienced bacteremia (n = 24 or candidemia (n = 1. Overall 41 (68% of 60 patients had polymicrobial infection. Escherichia coli (25% was the most common micro-organism isolated, followed by Enterococcus species (22%, Klebsiella pneumoniae (13%, and Bacteroides species (11%. Twenty-five (34% of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067. Four (5% patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years (p = 0.015 and patients with shock (p<0.001 had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016. CONCLUSION: Perianal infections were common and had high recurrence rate in adult patients with acute

  3. Unusual massive bone marrow fibrosis in acute promyelocytic leukemia following arsenic trioxide therapy

    Venkatesan, S.; Purohit, Abhishek; Ahuja, Ankur; Chandra, Dinesh; Aggarwal, Mukul; Amrita, R.; Kumar, Ravi; Mahapatra, Manoranjan; Pati, Hara P.; Tyagi, Seema

    2015-01-01

    Bone marrow fibrosis has been associated with different types of non-neoplastic conditions like granulomatous and autoimmune diseases and a variety of neoplastic disorders such as acute megakaryoblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma and myeloproliferative neoplsms. Therapy induced fibrosis is a rare phenomenon. Here we report a case of an incidentally diagnosed acute promyelocytic leukemia (APL) with t(11;17) which was treated with arsenic trioxide (ATO) for 45 days. However, the patient did not go into remission and developed massive fibrosis of bone marrow. Literature search does not reveal such documented marrow fibrosis following therapy with ATO in a case of APL. PMID:26716080

  4. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

    Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

    2007-01-01

    At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs of cardiomyo......At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs of...

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

    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...... more 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...

  6. A rare case of Acute Lymphocytic Leukemia (ALL presenting with double Philadelphia chromosome: relapse or secondary leukemia?

    Mireille Guimarães Vaz de Campos

    2003-01-01

    Full Text Available The Philadelphia chromosome is observed in 5% of pediatric acute lymphocytic leukemia (ALL and in 25% to 50% of adult ALL cases, and is associated with poor prognosis. Double Ph in a hyperdiploid karyotype is common in chronic myeloid leukemia (CML, but rarely found in ALL. We report here the case of a girl diagnosed with ALL at 7 years of age. After treatment with the pediatric protocol BFM 83 for ALL, she stayed in continuous complete remission for nine years. At age 19, she was re-admitted with a white blood cell count of 6.8 x 10(9/L with 3% blasts, and a platelet count of 65 x 109/L. Bone marrow aspirate showed 92.6% lymphoid blast cells, and chromosome analysis after G-banding revealed the karyotype 51,XX,+?5,t(9;22(q34.1;q11.2,+16,+20,+21,+der(22t(9;22(q34.1;q11.2 [10]/46,XX[1]. FISH analysis for the BCR/ABL fusion showed 56% of interphase cells with two fusion signals, 30% with one, and 6% with three. Double Ph is rare in relapsed leukemia, and the possibility of secondary leukemia cannot be ruled out.

  7. Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia

    Gustafsson, Britt; Hellebostad, Marit; Ifversen, Marianne;

    2011-01-01

    Juvenile myelomonocytic leukemia is a rare hematopoietic stem cell disease in children with features of both myelodysplasia and myeloproliferation. Extramedullary involvement has been reported and pulmonary involvement secondary to leukemic infiltration is an initial manifestation, which may result...

  8. Acute Respiratory Failure in 3 Children With Juvenile Myelomonocytic Leukemia

    Gustafsson, Britt; Hellebostad, Marit; Ifversen, Marianne;

    2011-01-01

    Juvenile myelomonocytic leukemia is a rare hematopoietic stem cell disease in children with features of both myelodysplasia and myeloproliferation. Extramedullary involvement has been reported and pulmonary involvement secondary to leukemic infiltration is an initial manifestation, which may result...

  9. Prevention of meningeal relapses in acute lymphoblastic leukemia

    The paper describes modern methods of preventing meningeal leukemia which, in view of the noxiousness of skull radiotherapy, increasingly restrict the use of this method in a growing number of children.(author)

  10. Contribution of Flow Cytometry to Acute Leukemia Classification in Tunisia

    S. Feki

    2000-01-01

    Full Text Available The precision of immunological characterization of leukemias was improved by a certain number of technical innovations, particularly hybridoma production and standardization, resulting in monoclonal antibodies and definition of recognised cellular antigens (designated by CD: Cluster of Differentiation.

  11. Unraveling Glucocorticoid Resistance In MLLrearranged Infant Acute Lymphoblastic Leukemia

    Hagelstein, Jill

    2014-01-01

    markdownabstract__Abstract__ In the Netherlands, approximately 650 children aged between 0 and 18 years are diagnosed with cancer every year, including ~120 patients suffering from leukemia. Leukemia (Greek for leukos - white, and haima for blood) is a type of cancer characterized by an abnormal increase of immature (non-functional) white blood cells in the bone marrow. As a result, the production of all healthy, functional blood cells is impaired, leading to anemia (loss of functional red bl...

  12. The ruthenium complex cis-(dichloro)tetraammineruthenium(III) chloride presents selective cytotoxicity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) tumor cell lines.

    Silveira-Lacerda, Elisângela de Paula; Vilanova-Costa, Cesar Augusto Sam Tiago; Hamaguchi, Amélia; Pavanin, Luiz Alfredo; Goulart, Luiz Ricardo; Homsi-Brandenburgo, Maria Inês; Dos Santos, Wagner Batista; Soares, Andreimar Martins; Nomizo, Auro

    2010-06-01

    The aim of present study was to verify the in vitro antitumor activity of a ruthenium complex, cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) toward different tumor cell lines. The antitumor studies showed that ruthenium(III) complex presents a relevant cytotoxic activity against murine B cell lymphoma (A-20), murine ascitic sarcoma 180 (S-180), human breast adenocarcinoma (SK-BR-3), and human T cell leukemia (Jurkat) cell lines and a very low cytotoxicity toward human peripheral blood mononuclear cells. The ruthenium(III) complex decreased the fraction of tumor cells in G0/G1 and/or G2-M phases, indicating that this compound may act on resting/early entering G0/G1 cells and/or precycling G2-M cells. The cytotoxic activity of a high concentration (2 mg mL(-1)) of cis-[RuCl(2)(NH(3))(4)]Cl toward Jurkat cells correlated with an increased number of annexin V-positive cells and also the presence of DNA fragmentation, suggesting that this compound induces apoptosis in tumor cells. The development of new antineoplastic medications demands adequate knowledge in order to avoid inefficient or toxic treatments. Thus, a mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success and to the rational design of new compounds with improved potency. PMID:19727575

  13. The apoptosis-inducing activity towards leukemia and lymphoma cells in a cyanobacterial culture collection is not associated with mouse bioassay toxicity

    Oftedal, Linn; Skjærven, Kaja H.; Coyne, Rosie T.; Edvardsen, Bente; Rohrlack, Thomas; Skulberg, Olav M.; Døskeland, Stein Ove; Herfindal, Lars

    2010-01-01

    Cyanobacteria (83 strains and seven natural populations) were screened for content of apoptosis (cell death)-inducing activity towards neoplastic cells of the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured for decades, and was unrelated to whether the cyanobacteria had been collected from polar, temperate, or tropic environments. The activity was more abundant in the genera Anabaena and Mi...

  14. Identification of functional cooperative mutations of SETD2 in human acute leukemia

    Zhu, Xiaofan; He, Fuhong; Zeng, Huimin; Ling, Shaoping; Chen, Aili; Wang, Yaqin; Yan, Xiaomei; Wei, Wei; Pang, Yakun; Cheng, Hui; Hua, Chunlan; Zhang, Yue; Yang, Xuejing; Lu, Xin; Cao, Lihua; Hao, Lingtong; Dong, Lili; Zou, Wei; Wu, Jun; Li, Xia; Zheng, Si; Yan, Jin; Zhou, Jing; Zhang, Lixia; Mi, Shuangli; Wang, Xiaojuan; Zhang, Li; Zou, Yao; Chen, Yumei; Geng, Zhe; Wang, Jianmin; Zhou, Jianfeng; Liu, Xin; Wang, Jianxiang; Yuan, Weiping; Huang, Gang; Cheng, Tao; Wang, Qian-fei

    2015-01-01

    Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy1,2, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene3 and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase)4. Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development. PMID:24509477

  15. Extramedullary Relapse of Acute Myeloid and Lymphoid Leukemia in Children: A Retrospective Analysis

    Jee Young Kim

    2016-05-01

    Full Text Available Background Extramedullary relapse (EMR is a recurrence of leukemia in sites other than the bone marrow, and it exhibits a relatively rare presentation of relapse of acute leukemia. However, EMR is an important cause of treatment failure among patients with acute leukemia. Therefore, early detection of these relapses may improve the prognosis. Objectives To describe the disease-related demographic and clinical features and radiologic findings for children diagnosed with EMR in acute leukemia. Patients and Methods The study was based on 22 children (M: F = 14: 8; mean age 7.30 (2.1 - 15.7 years with 8 acute myeloid leukemia (AML and 14 acute lymphoid leukemia (ALL who had experienced an EMR. Age, gender, clinical symptoms, initial extramedullary disease (EMD, French-American-British (FAB morphology, cytogenetics, time to and site of EMR, concurrent bone marrow relapse (BMR, radiologic findings, and outcomes were evaluated. Results No definite relationship was found between initial EMD and EMR. A predilection for AML to relapse in the central nervous system (CNS, except for the CSF and bone, and for ALL to relapse in the CSF and kidney seemed to occur. Patients with EMR had a significantly higher incidence of t(8: 21 cytogenetics and FAB M2 and L1 morphologies. EMR accompanied with concurrent BMR occurred in 31.8% of the patients, who exhibited a relatively grave clinical course. Radiologic findings were nonspecific and had a great variety of structure involved, including bulging enhancing mass in the CT scan, hypoechoic mass in the US, and enhanced mass-like lesion in the MRI. Conclusions Knowledge of the potential sites of EMR, their risk factors, and their clinical and radiologic features may be helpful in the early diagnosis of relapse and planning for therapy.

  16. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline; Guièze, Romain; Himberlin, Chantal; Randriamalala, Edouard; Preudhomme, Claude; Jourdan, Eric; Dombret, Hervé; Ifrah, Norbert

    2015-01-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18–60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12). PMID:25715404

  17. Inter-Platform comparability of microarrays in acute lymphoblastic leukemia

    Mintz Michelle

    2004-09-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS rates improving from 80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21[TEL-AML1], t(4;11[MLL-AF4], t(9;22[BCR-ABL], and t(1;19[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. Results We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors

  18. Significance of Neuropilin-1 Expression in Acute Myeloid Leukemia

    Tarif H. Sallam

    2013-09-01

    Full Text Available Objective: Neuropilin-1 is a vascular endothelial growth factor receptor that acts as a mediator of angiogenesis. Its importance in hematological malignancies such as acute myeloid leukemia (AML remains to be elucidated. The aim of this study was to evaluate the significance of neuropilin-1 expression in AML patients by both flow cytometry and real-time polymerase chain reaction (PCR in regard to its diagnostic and prognostic values. Materials and Methods: Bone marrow aspirates of 44 patients with de novo AML and 12 relapsed AML patients were examined in this study. Ten subjects with nonhematological malignancy serving as the control group were also included. Results: Neuropilin-1 expression by flow cytometry showed a highly significant increase in de novo and relapsed AML patients with a mean of 27.1±17.5% and 21.5±16.6%, respectively, compared to control group’s mean of 3.4±1.9%. A cut-off value of 6% was established as differentiating patients from the control group. By real-time PCR, no statistical significance was found in de novo and relapsed AML patients with a mean of 1.9±3.6 IU/L and 0.3±0.2 IU/L, respectively, compared to the control group’s mean of 0.3±0.1 IU/L. Neuropilin-1 surface expression by flow cytometry showed a significant correlation with total leukocyte count and a negative correlation with hemoglobin level in de novo AML patients. In relapsed AML patients, positive significant correlations were found with age, bone marrow blast percentage, and CD14. Neuropilin-1 mRNA level by real-time PCR showed a positive significant correlation with peripheral blood blast percentage and CD117 and a negative correlation with hemoglobin level in de novo AML patients. In relapsed patients, a positive correlation was found with lactate dehydrogenase. Conclusion: Neuropilin-1 can be used as a tool for diagnosis and prognosis in AML patients.

  19. Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia

    In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia, acute leukemia in relapse, acute leukemia in remission or chronic myeloid leukemia. The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% with a median observation time of 40 months. For patients grafted in the first consecutive remission of ALL the survival rate is 42% with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%. (orig.)

  20. Myeloid Sarcoma Presenting with Leukemoid Reaction in a Child Treated for Acute Lymphoblastic Leukemia

    Aylin Canbolat Ayhan

    2014-01-01

    Full Text Available Background. Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia. Case Presentation. A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm3. FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma. Conclusion. Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.

  1. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  2. Clinical significance of microRNAs in chronic and acute human leukemia.

    Yeh, Chien-Hung; Moles, Ramona; Nicot, Christophe

    2016-01-01

    Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID:27179712

  3. Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia

    In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved

  4. JAK-2V617F Mutation in Acute Leukemia (South Egypt Experience)

    Badrawy Hosny; Ibrahim Abeer

    2013-01-01

    Aim: To search for JAK2V617F mutation in patients with acute myeloid and acute lymphoblastic leukemia in south Egypt. Study Design: JAK2V617F mutation detected by amplification refractory mutation system (ARMS) -PCR. Place and Duration of Study: Department of clinical pathology and department of medical oncology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt, between December 2010 and December 2012. Method: We included 90 patients (58 men and 32 women; ag...

  5. Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia

    Chotai, Pranit N.; Kasangana, Kalenda; Abhinav B. Chandra; Atul S Rao

    2016-01-01

    Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We r...

  6. Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11 leukemia with lineage switch and extreme leukocytosis

    Čolović Nataša

    2015-01-01

    Full Text Available Introduction. In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. Case Outline. In April of 2012 a 37-year-old male presented with bilateral deep leg vein thrombosis and malaise. Laboratory data were as follows: Hb 118 g/L, WBC 354x109/L (with 91% blasts in differential leukocyte count, platelets 60Ч109/L. Bone marrow aspirate and immunophenotype revealed the presence of acute lymphoblastic leukemia. Cytogenetic analysis was as follows: 46,XY,t(4;11(q21:q23 [2]/62-82,XY,t(4;11[18]. Molecular analysis showed MLL-AF4 rearrangement. The patient was on low molecular weight heparin and combined chemotherapy according to protocol HyperCVAD. On day 10 after chemotherapy he got chest pain. Three days later AMI was diagnosed (creatine kinase 66 U/L, CK-MB 13U/L, troponin 1.19 μg/L. Electrocardiogram showed the ST elevation in leads D1, D2, aVL, V5 and V6 and “micro q” in D1. On echocardiography, hypokinesia of the left ventricle and ejection fraction of 39% was found. After recovering from AMI and restoring left ventricle ejection fraction to 59%, second course of HyperCVAD was given. The control bone marrow aspirate showed 88% of blasts but with monoblastic appearance. Flow cytometry confirmed a lineage switch from lymphoblasts to monoblasts. In further course of the disease he was treated with a variety of chemotherapeutic combinations without achieving remission. Eventually, palliative chemotherapy was administered to reduce the bulk of blasts. He died five months after the initial diagnosis. Conclusion. AMI in young adults with acute leukemia is a very rare complication

  7. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  8. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    D. Schotte (Diana); R.X. de Menezes (Renee); F. Akbari Moqadam (Farhad); L.M. Khankahdani (Leila Mohammadi); E.A.M. Lange-Turenhout (Ellen); C. Chen (Caifu); R. Pieters (Rob); M.L. den Boer (Monique)

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression

  9. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia

    M. Jongen-Lavrencic (Mojca); S.M. Sun; M.K. Dijkstra; P.J.M. Valk (Peter); B. Löwenberg (Bob)

    2008-01-01

    textabstractAcute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed

  10. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    Hulleman, Esther; Kazemier, Karin; Holleman, Amy; VanderWeele, David; Rudin, Charles; Broekhuis, Mathilde; Evans, William; Pieters, Rob; Boer, M.L.D.

    2009-01-01

    textabstractTreatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant precursor B-lineage leukemic patients. Here, we show that prednisolone resistance is associated with increased glucose consumption and that inhibition of glycolysis sensitizes prednisolon...

  11. Epigenetic regulators and their impact on therapy in acute myeloid leukemia.

    Pastore, Friederike; Levine, Ross L

    2016-03-01

    Genomic studies of hematologic malignancies have identified a spectrum of recurrent somatic alterations that contribute to acute myeloid leukemia initiation and maintenance, and which confer sensitivities to molecularly targeted therapies. The majority of these genetic events are small, site-specific alterations in DNA sequence. In more than two thirds of patients with de novo acute myeloid leukemia mutations epigenetic modifiers are detected. Epigenetic modifiers encompass a large group of proteins that modify DNA at cytosine residues or cause post-translational histone modifications such as methylations or acetylations. Altered functions of these epigenetic modifiers disturb the physiological balance between gene activation and gene repression and contribute to aberrant gene expression regulation found in acute myeloid leukemia. This review provides an overview of the epigenetic modifiers mutated in acute myeloid leukemia, their clinical relevance and how a deeper understanding of their biological function has led to the discovery of new specific targets, some of which are currently tested in mechanism-based clinical trials. PMID:26928248

  12. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui;

    2013-01-01

    While all-trans retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) has been the paradigm of targeted therapy for oncogenic transcription factors, the underlying mechanisms remain largely unknown, and a significant number of patients still relapse and become ATRA resistant. We...

  13. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

    Bohnstedt, C; Levinsen, M; Rosthøj, S;

    2013-01-01

    Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology and...

  14. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette;

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  15. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

    Nordlund, Jessica; Bäcklin, Christofer L; Zachariadis, Vasilios;

    2015-01-01

    BACKGROUND: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA...

  16. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  17. Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia

    Balgobind, Brian V.; Van den Heuvel-Eibrink, Marry M.; De Menezes, Renee X.; Reinhardt, Dirk; Hollink, Iris H. I. M.; Arentsen-Peters, Susan T. J. C. M.; van Wering, Elisabeth R.; Kaspers, Gertjan J. L.; Cloos, Jacqueline; de Bont, Evelien S. J. M.; Cayuela, Jean-Michel; Baruchel, Andre; Meyer, Claus; Marschalek, Rolf; Trka, Jan; Stary, Jan; Beverloo, H. Berna; Pieters, Rob; Zwaan, C. Michel; den Boer, Monique L.

    2011-01-01

    Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the

  18. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  19. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil;

    2016-01-01

    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML...

  20. PHARMACOKINETICS OF VINCRISTINE IN CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOCYTIC-LEUKEMIA

    CROM, WR; DEGRAAF, SSN; SYNOLD, T; UGES, DRA; BLOEMHOF, H; RIVERA, G; CHRISTENSEN, ML; MAHMOUD, H; EVANS, WE

    1994-01-01

    We studied the pharmacokinetics of vincristine in children with acute lymphocytic leukemia by means of a specific high-performance liquid chromatographic assay with ultraviolet and electrochemical detection and a limited sampling strategy. Our objectives were to characterize the disposition of vincr