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Sample records for acute promyelocytic leukemia

  1. Genetics Home Reference: acute promyelocytic leukemia

    Science.gov (United States)

    ... Home Health Conditions Acute promyelocytic leukemia Acute promyelocytic leukemia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Acute promyelocytic leukemia is a form of acute myeloid leukemia, a ...

  2. Pneumatosis Intestinalis in a Patient with Acute Promyelocytic Leukemia

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    Abhishek Mangaonkar

    2015-01-01

    Full Text Available Pneumatosis Intestinalis is a rare condition characterized by the presence of gas within the intestinal wall. We describe a case of a 33-year-old woman with acute promyelocytic leukemia who developed nausea and nonbloody diarrhea. CT showed intramural air in transverse and descending colon. Patient clinically improved with conservative management.

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

    Science.gov (United States)

    2017-07-18

    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

  4. HISTORY OF ACUTE PROMYELOCYTIC LEUKEMIA: A TALE OF ENDLESS REVOLUTION

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    Francesco Lo-Coco

    2011-12-01

    Full Text Available Only few thousand people are diagnosed each year of Acute Promyelocytic Leukemia (APL worldwide. However, for a number of reasons such rare disease is regarded as a paradigm in the entire field of medicine. Once considered the most malignant human leukemia as well as the one associated with the worst prognosis, APL has been transformed in the past few decades into the most frequently curable one. This extraordinary progress has been the result of an unprecedented coincidence of advances in both biological and clinical research.

  5. Cellulitis with Leukocytopenia as an Initial Sign of Acute Promyelocytic Leukemia

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    Sachiko Sakamoto

    2012-03-01

    Full Text Available Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3 is caused by translocation of reciprocal chromosomal rearrangement t(15;17, which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia.

  6. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

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    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.

  7. RARA fusion genes in acute promyelocytic leukemia: a review.

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    De Braekeleer, Etienne; Douet-Guilbert, Nathalie; De Braekeleer, Marc

    2014-06-01

    The t(15;17)(q24;q21), generating a PML-RARA fusion gene, is the hallmark of acute promyelocytic leukemia (APL). At present, eight other genes fusing with RARA have been identified. The resulting fusion proteins retain domains of the RARA protein allowing binding to retinoic acid response elements (RARE) and dimerization with the retinoid X receptor protein (RXRA). They participate in protein-protein interactions, associating with RXRA to form hetero-oligomeric complexes that can bind to RARE. They have a dominant-negative effect on wild-type RARA/RXRA transcriptional activity. Moreover, RARA fusion proteins can homodimerize, conferring the ability to regulate an expanded repertoire of genes normally not affected by RARA. RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signalling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of ATRA or arsenic trioxide. However, resistance to these two drugs is a major problem, which necessitates development of new therapies.

  8. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

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    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.

  9. Phosphatidylserine exposure and procoagulant activity in acute promyelocytic leukemia.

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    Zhou, J; Shi, J; Hou, J; Cao, F; Zhang, Y; Rasmussen, J T; Heegaard, C W; Gilbert, G E

    2010-04-01

    Acute promyelocytic leukemia (APL) frequently causes disseminated intravascular coagulation that can worsen with cytotoxic chemotherapy but improve with the therapeutic differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). APL cells display tissue factor but the relationship of tissue factor and other procoagulant activity to phosphatidylserine (PS) exposure is largely unknown. Lactadherin, a milk protein with stereospecific binding to phosphatidyl-L-serine, was used as a probe for PS exposure on an immortalized APL cell line (NB4) and on the cells of eight patients with APL. PS exposure was evaluated with flow cytometry, confocal microscopy, coagulation assays, and purified prothrombinase and factor (F) Xase assays. Plasma procoagulant activity of NB4 and APL cells increased approximately 15-fold after exposure to etoposide or daunorubicin and decreased 80% after treatment with ATRA or As(2)O(3). Procoagulant activity corresponded to exposed PS on viable APL cells. PS exposure decreased after treatment with ATRA or As(2)O(3) and increased after treatment with daunorubicin or etoposide. Excess lactadherin inhibited 80-85% of intrinsic FXase, FVIIa-tissue factor and prothrombinase activities on both NB4 cells and APL cells. Confocal microscopy identified membrane patches that stained with lactadherin, but not annexin V, demonstrating focal, low-level PS exposure. PS is exposed on viable APL cells and is necessary for approximately 80% of procoagulant activity.

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

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    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.

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

    LENUS (Irish Health Repository)

    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.

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

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    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.

  13. A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Marstrand, T T; Borup, R; Willer, A

    2010-01-01

    Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges as a conseque......Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges...... regulation, and (ii) the identification of candidate drugs and drug targets for therapeutic interventions. Significantly, our study provides a conceptual framework that can be applied to any subtype of AML and cancer in general to uncover novel information from published microarray data sets at low cost....... In a broader perspective, our study provides strong evidence that genomic strategies might be used in a clinical setting to prospectively identify candidate drugs that subsequently are validated in vitro to define the most effective drug combination for individual cancer patients on a rational basis....

  14. CNS relapse in a low risk acute promyelocytic leukemia patient treated with ATRA-based regimen: is there a role for prophylactic CNS therapy in acute promyelocytic leukemia?

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    Gangadharan, K. V.; Prabhu, Raghuveer; Mampilly, Neena

    2009-01-01

    Though the incidence of CNS relapse in acute promyelocytic leukemia (AML-M3 FAB classification) has increased following the advent of all-trans retinoic acid (ATRA), still CNS relapse accounts for only 2–3% of all relapses in AML-M3 trated with standard ATRA plus chemotherapy regimen. We report a case of low risk AML-M3 treated with standard therapy, developing CNS relapse while on maintenance therapy with ATRA + 6-mercaptopurine (6-MP) + methotrexate (MTX).

  15. Hypercalcemia and acute pancreatitis in a male patient with acute promyelocytic leukemia and pulmonary tuberculosis.

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    Abdullah, Ali S; Adel, Ahmad M; Hussein, Radwa M; Abdullah, Mohammed Aj; Yousaf, Anil; Mudawi, Deena; Mohamed, Shehab F; Nashwan, Abdulqadir J; Soliman, Dina; Ibrahim, Feryal; Yassin, Mohamed A

    2018-04-03

    We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

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

    NARCIS (Netherlands)

    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

  17. Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin.

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    Lavallée, Vincent-Philippe; Chagraoui, Jalila; MacRae, Tara; Marquis, Miriam; Bonnefoy, Arnaud; Krosl, Jana; Lemieux, Sébastien; Marinier, Anne; Pabst, Caroline; Rivard, Georges-Étienne; Hébert, Josée; Sauvageau, Guy

    2018-02-23

    Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor. Most intriguingly, the Podoplanin (PDPN) gene, involved in platelet aggregation, is aberrantly expressed in APL promyelocytes and is the most distinctive transcript for this disease. Using an antibody panel optimized for AML diagnosis by flow cytometry, we also found that PDPN was the most specific surface marker for APL, and that all-trans retinoic acid therapy rapidly decreases its expression. Functional studies showed that engineered overexpression of this gene in human leukemic cells causes aberrant platelet binding, activation and aggregation. PDPN-expressing primary APL cells, but not PDPN-negative primary leukemias, specifically induce platelet binding, activation and aggregation. Finally, PDPN expression on leukemia cells in a xenograft model was associated with thrombocytopenia and prolonged bleeding time in vivo. Together our results suggest that PDPN may contribute to the hemostatic perturbations found in APL.

  18. Recurrent Arterial and Venous Thromboemboli as Initial Presentation of Acute Promyelocytic Leukemia

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    Trottier-Tellier, Felix; Durand, Madeleine; Kolan, Christophe; Wistaff, Robert; Nguyen, Paul Van; Laskine, Mikhael

    2014-01-01

    We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic arterial and venous thrombosis as an initial presentation of an acute promyelocytic leukemia (APL). After the diagnosis, the patient was treated with all trans-retinoic acid and arsenic chemotherapy concomitant to systemic anticoagulation. This treatment regimen led to a complete remission and absence of relapse of the thrombosis or APL during the follow-up. To our knowledge, this presentation is the second case in ...

  19. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

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    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

  20. The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies.

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    de Thé, Hugues; Le Bras, Morgane; Lallemand-Breitenbach, Valérie

    2012-07-09

    Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.

  1. Recurrent Arterial and Venous Thromboemboli as Initial Presentation of Acute Promyelocytic Leukemia

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    Trottier-Tellier, Felix; Durand, Madeleine; Kolan, Christophe; Wistaff, Robert; Nguyen, Paul Van; Laskine, Mikhael

    2014-01-01

    We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic arterial and venous thrombosis as an initial presentation of an acute promyelocytic leukemia (APL). After the diagnosis, the patient was treated with all trans-retinoic acid and arsenic chemotherapy concomitant to systemic anticoagulation. This treatment regimen led to a complete remission and absence of relapse of the thrombosis or APL during the follow-up. To our knowledge, this presentation is the second case in the literature. We use this opportunity to emphasize the importance of performing a complete medical evaluation in cases of unusual thromboembolic events. PMID:25110545

  2. Managing acute promyelocytic leukemia in patients belonging to the Jehovah’s Witness congregation

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    Anand P. Jillella

    2017-09-01

    Full Text Available Acute promyelocytic leukemia (APL is a hyper-acute leukemia and presents with cytopenias and disseminated intravascular coagulation. Jehovah’s Witnesses with APL offer a unique challenge during induction by refusing transfusion and pose a difficult challenge in this curable disease. Our focus over the last 8 years has been decreasing early deaths in APL in both academic and community centers. As a result we have extensive experience in APL induction with a proven improvement in early deaths. Three patients with APL belonging to the Jehovah’s Witness congregation were treated in our practice and published literature in treating Witnesses with APL was reviewed. It is highly imperative to prevent induction mortality in this patient population. The goal of treatment among the Witnesses is to prevent death during induction and subsequently cure them. We discuss the management and proactive measures to prevent induction mortality in this most curable blood cancer.

  3. Advances in the management of acute promyelocytic leukemia and other hematologic malignancies with arsenic trioxide.

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    Slack, James L; Waxman, Samuel; Tricot, Guido; Tallman, Martin S; Bloomfield, Clara D

    2002-01-01

    Acute promyelocytic leukemia (APL), once considered the most devastating subtype of acute myeloid leukemia, is now the most treatable of all subtypes as a result of intensive research into its molecular pathogenesis. This research has led to a rational approach to treatment in which the use of the differentiating agent all-trans-retinoic acid (ATRA) has proven to be effective first-line treatment for inducing complete remission. Arsenic trioxide (ATO) is currently used to treat relapsed disease, further enhancing survival rates in a patient population for which limited salvage options exist. This review discusses the molecular mechanisms responsible for development of APL and the evolution of treatment options over the last three decades, including the major advances using ATRA and ATO in the last 12 years. The mechanism of action of ATO is also described in view of this agent's potential for broader therapeutic application in a variety of hematologic malignancies.

  4. Cryptic PML-RARα positive acute promyelocytic leukemia with unusual morphology and cytogenetics

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    Goyal Manu

    2010-10-01

    Full Text Available Acute Promyelocytic Leukemia (APL is different from other forms of acute myeloid leukemia (AML, to the reason being the potential devastating coagulopathy and the sensitivity to all-trans retinoic acid (ATRA and arsenic trioxide (As 2 O 3 . We hereby present a case of APL, morphologically distinct from the hypergranular APL; however, the flow cytometry revealed a characteristic phenotype showing dim CD45, bright CD13, bright CD33 and dim CD117 positivity. These were negative for CD34, HLA-DR, B-lymphoid and T-lymphoid lineage markers. Conventional cytogenetics revealed a distinct karyotype of a male with translocation t(4;15(q34.2:q26.3. However, interphase florescence-in-situ hybridization (FISH revealed PML/RARA fusion signal on chromosome 15 in 90% cells. The cryptic translocations may be missed on conventional cytogenetics, however, need to be picked by other techniques as FISH.

  5. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

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    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  6. PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.

    Science.gov (United States)

    Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun

    2017-10-01

    Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    NARCIS (Netherlands)

    P. Montesinos (Pau); J. Díaz-Mediavilla (Joaquín); G. Debén (Guillermo); V. Prates (Virginia); M. Tormo (Mar); V. Rybio (Vicente); I. Pérez (Inmaculada); I. Fernández (Isolda); M. Viguria (Maricruz); C. Rayón (Chelo); J. de Serna (Javier); J. Esteve (Jordi); J.M. Bergua (Juan Miguel); C. Rivas (Concha); J.D. González (José David); M. González (Marcos); S. Negri (Silvia); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractBackground: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic

  8. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

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    de Botton, S; Sanz, M A; Chevret, S; Dombret, H; Martin, G; Thomas, X; Mediavilla, J D; Recher, C; Ades, L; Quesnel, B; Brault, P; Fey, M; Wandt, H; Machover, D; Guerci, A; Maloisel, F; Stoppa, A M; Rayon, C; Ribera, J M; Chomienne, C; Degos, L; Fenaux, P

    2006-01-01

    We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age or = 10,000/ mm3) (P or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.

  9. Acute promyelocytic leukemia with JAK2 V617F and severe differentiation syndrome

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    Theodore P. Braun

    2015-01-01

    Full Text Available Myeloproliferative neoplasms transformed into AML usually have a poor prognosis. We report a case of essential thrombocythemia with myelofibrosis that transformed into acute promyelocytic leukemia (APL with both the t(15;17 translocation as well as the JAK2 V617F mutation. Clinically, this case was notable for severe differentiation syndrome despite treatment with high-dose dexamethasone. Cytokine production by differentiating APL cells was not directly abrogated by JAK2 inhibitors in vitro, suggesting that JAK2 V617F enhances the hyperinflammatory response downstream of cytokines. JAK1/2 inhibitors may therefore dampen the inflammatory cascade downstream of cytokine production, similar to glucocorticoids, and have a role in treating severe differentiation syndrome.

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

    Science.gov (United States)

    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.

  11. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  12. Rare presentation of pediatric acute promyelocytic leukemia as multiple lytic bone lesions: Case report and review of literature

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    Manjusha Nair

    2014-01-01

    Full Text Available Acute promyelocytic leukemia (APL is an uncommon malignancy in the pediatric population, accounting for only 5-10% of pediatric acute myeloid leukemias, and for this disease to present with bone lesions at diagnosis is extremely unusual. We wish to convey that very rarely, in a pediatric cancer patient presenting with multiple extensive lytic bone lesions, the diagnosis can be APL. The treatment protocol and prognostic implications are vastly different. Histopathology is the gold standard in arriving at a correct diagnosis and delivering proper treatment in such cases. This patient had excellent response to chemotherapy.

  13. Microgranular acute promyelocytic leukemia presenting with leukopenia and an unusual immunophenotype.

    Science.gov (United States)

    McDonnell, Megan H; Smith, Elton T; Lipford, Edward H; Gerber, Jonathan M; Grunwald, Michael R

    2017-03-01

    The microgranular variant (M3v) of acute promyelocytic leukemia (APL) is rare, and the diagnosis can be delayed due to variability in how this condition presents. M3v blasts often have folded nuclei, but unlike traditional APL blasts, they often possess faint granules without Auer rods. In addition, microgranular APL often presents with an elevated or normal white blood cell count in contrast with the leukopenia seen in traditional APL. In APL, delayed diagnosis can lead to early death from disseminated intravascular coagulation (DIC), which is the main cause of mortality in an otherwise treatable, and often curable, leukemia. We describe a 19-year-old male with microgranular APL who presented with leukopenia and many blasts resembling non-APL AML blasts with an unexpected immunophenotypic pattern. He was treated for DIC and initiated on all-trans-retinoic acid and arsenic trioxide; he achieved complete molecular remission after induction therapy. Suspicion for APL should always remain high in the presence of clinical manifestations of the disease in order that appropriate treatment can be initiated rapidly to prevent early death. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  14. [Relapse of acute promyelocytic leukemia in the central nervous system revealed by isolated dementia].

    Science.gov (United States)

    Colin, O; Julian, A; Puyade, M; Bouyer, S; Meurin, E; Blondeau, S; Houeto, J L; Neau, J P

    2016-12-01

    Approximately 1.5% of dementia is due to curable aetiology. We report an isolated dementia syndrome due to a meningeal relapse of acute promyelocytic leukaemia with favourable outcome after appropriate treatment. A 72-year-old woman, in remission of an acute promyelocytic leukaemia, presented a loss of autonomy for several months due to corticosubcortical dementia. Lumbar puncture showed blast cells indicating meningeal relapse of leukaemia. Intrathecal chemotherapy and arsenic trioxide obtained biological and molecular remission as well as restoration of normal cognitive functions. In patients with hematologic past history such as acute promyelocytic leukaemia, an isolated cognitive impairment should alert physicians to search for an isolated neuromeningeal relapse. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

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    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  16. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH HIGH WHITE CELL BLOOD COUNTS.

    Directory of Open Access Journals (Sweden)

    Charicleia Kelaidi

    2011-09-01

    Full Text Available Acute promyelocytic leukemia (APL with WBC above 10 G/L has long been considered, even in the all-trans retinoic acid (ATRA era, to carry a relatively poor prognosis (compared to  APL with WBC below 10 G/L, due to increased early mortality and relapse. However, early deaths can to a large extent be avoided if specific measures are rapidly instigated, including prompt referral to a specialized center, immediate onset of ATRA and chemotherapy, treatment of coagulopathy with adequate platelet transfusional support, and prevention and management of differentiation syndrome. Strategies to reduce relapse rate include chemotherapy reinforcement with cytarabine and/or arsenic trioxide during consolidation, prolonged maintenance treatment, especially with ATRA and low dose chemotherapy, and possibly, although this is debated, intrathecal prophylaxis to prevent central nervous system relapse. By applying those measures, outcomes of patients with high risk APL have considerably improved, and have become in many studies almost similar to those of standard risk APL patients.

  17. Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.

    Science.gov (United States)

    Moradzadeh, Maliheh; Tabarraei, Alijan; Sadeghnia, Hamid Reza; Ghorbani, Ahmad; Mohamadkhani, Ashraf; Erfanian, Saiedeh; Sahebkar, Amirhossein

    2018-02-01

    Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 μM) and all-trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients. © 2017 Wiley Periodicals, Inc.

  18. PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells.

    Science.gov (United States)

    Fang, Yi; Garnier, Delphine; Lee, Tae Hoon; D'Asti, Esterina; Montermini, Laura; Meehan, Brian; Rak, Janusz

    2016-01-01

    Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre-treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy.

  19. Evidence of functional interaction between NuMA-RARalpha and RXRalpha in an in vivo model of acute promyelocytic leukemia.

    Science.gov (United States)

    Sukhai, M A; Thomas, M; Xuan, Y; Chan, L S A; Hamadanizadeh, S A; Zhang, T; Bharadwaj, R R; Schuh, A C; Wells, R A; Kamel-Reid, S

    2008-08-07

    Acute promyelocytic leukemia (APL) is characterized by reciprocal balanced chromosomal translocations involving retinoic acid receptor-alpha (RARalpha). RARalpha heterodimerizes with the retinoid X receptor-alpha (RXRalpha) and transcriptionally regulates myeloid differentiation in response to ATRA (all-trans retinoic acid). Several lines of evidence suggest that APL fusion proteins interact with RXRalpha. To elucidate the role of RXRalpha in APL, we conditionally knocked out RXRalpha in the hCG-NuMA-RARalpha APL mouse model. Phenotype analysis of NuMA-RARalpha+ mice demonstrated that these mice developed a myeloproliferative disease-like myeloid leukemia within 4 months of birth. While hemizygous and homozygous RXRalpha conditional knockout mice were phenotypically normal as late as 12 months of age, we observed that the leukemic phenotype in NuMA-RARalpha+ mice was dependent on the presence of functional RXRalpha. Bone marrow promyelocyte counts were significantly reduced in NuMA-RARalpha+ mice with RXRalpha knocked down. Significant differences in the accumulations of Gr-1+ and Mac-1+ cells were also seen. We further observed that genes previously identified to be cooperating events in APL were also regulated in an RXRalpha-dependent manner. We therefore propose that the APL fusion protein NuMA-RARalpha cooperates with RXRalpha in the development of leukemia in hCG-NuMA-RARalpha transgenic mice and suggest a novel role for RXRalpha in the pathogenesis of APL.

  20. [Chronic hepatic damage in acute promyelocytic leukemia patients treated with tetra-arsenic tetra-sulfide].

    Science.gov (United States)

    Qin, Xiao-ying; Jiang, Bin; Li, Guo-xuan; Lu, Dao-pei

    2006-04-01

    To investigate the chronic hepatic damage in acute promyelocytic leukemia (APL) patients long-term treated with tetra-arsonic tetra-sulfide (As(4)S(4)). The periodical liver biochemical examinations and ultrasonography results and hepatic fibrosis indicators (P III NP and type IV collagen) of patients were analysed. 106 APL patients treated with As(4)S(4), the median follow-up time was 36 months (6 - 72). The HCV(-) group includes 84 APL patients. During the first course the abnormal rate of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 16.7% and 14.5% (higher than the two times of the normal value), the ALT, AST, gamma-glyoxylate aminotransferase (GGT) levels during the first course were statistically higher than As4S4 treatment before (P 0.05). Other biochemical indicators such as ALP, LDH, TBIL, DBIL, TP, ALB, A/G, BUN, CRE, there were no significantly differences before and after As(4)S(4) treatment (P > 0.05). The HCV(+) group includes 22 APL patients, during the first course, the abnormal rate of the ALT, AST were 63.6% and 59.1%, but at the 2 year, more than 3 years there were no significantly differences compared with As(4)S(4) treatment before (P > 0.05). 42 APL patients were treated with As(4)S(4) more than 3 years, in 33 HCV(-) APL patients, two APL patients had splenomegaly, one APL patient's breadth of the portal vein was wider than 1.4 cm, 21 APL patients had fatty liver (63.6%). The hepatic fibrosis indicators of the 16 APL patients were all normal. In 9 HCV(+) APL patients, 4 APL patients had splenomegaly, 2 APL patients, breadth of portal vein were wider than 1.4 cm, 6 APL patients had fatty liver (66.7%). 6 patients were examined with the hepatic fibrosis indicators, 2 patients, were higher than the normal value. Long term As(4)S(4) treatment for APL patients had no obvious effects on hepatic function, no obvious hepatic fibrosis and portal hypertension signs at more than 3 years, excepting for the rate of fatty liver

  1. Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

    NARCIS (Netherlands)

    Barragan, Eva; Montesinos, Pau; Camos, Mireia; Gonzalez, Marcos; Calasanz, Maria J.; Roman-Gomez, Jose; Gomez-Casares, Maria T.; Ayala, Rosa; Lopez, Javier; Fuster, Oscar; Colomer, Dolors; Chillon, Carmen; Larrayoz, Maria J.; Sanchez-Godoy, Pedro; Gonzalez-Campos, Jose; Manso, Felix; Amador, Maria L.; Vellenga, Edo; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and

  2. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char-

  3. Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy

    NARCIS (Netherlands)

    Martinez-Cuadron, D.; Montesinos, P.; Vellenga, E.; Bernal, T.; Salamero, O.; Holowiecka, A.; Brunet, S.; Gil, C.; Benavente, C.; Ribera, J. M.; Perez-Encinas, M.; De la Serna, J.; Esteve, J.; Rubio, V.; Gonzalez-Campos, J.; Escoda, L.; Amutio, M. E.; Arnan, M.; Arias, J.; Negri, S.; Lowenberg, B.; Sanz, M. A.

    Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk-and age-adapted protocol (Programa Espanol de

  4. Low platelet count is potentially the most important contributor to severe bleeding in patients newly diagnosed with acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Song Y

    2017-10-01

    Full Text Available Yu-hua Song,1,2 Peng Peng,3 Chun Qiao,1 Run Zhang,1 Jian-yong Li,1 Hua Lu1 1Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 2Department of Hematology, 3Department of Oncology, The Second Hospital of Nanjing, Nanjing, People’s Republic of China Abstract: The objective of the current study was to provide more appropriate therapeutic strategies for reducing severe hemorrhaging by assessing the recovery of abnormal coagulation indexes in patients with acute promyelocytic leukemia (APL during induction therapy. Retrospective analyses of 112 patients newly diagnosed with APL were performed during initial treatment. In our study, the early death rate was 5.36%. Hemorrhage was the leading cause of death during the induction period (4/6. The values of white blood cell count, lactate dehydrogenase, prothrombin time (PT, fibrinogen (Fbg, hemoglobin, and bone marrow leukemic promyelocytes were significantly different in the high-risk group compared to the low/intermediate-risk groups. There were significant differences in the white blood cell count, bone marrow leukemic promyelocytes, platelet (PLT count, and the levels of lactate dehydrogenase, d-dimer, PT, and Fbg, as well as in FLT3-ITD mutations between patients with major bleeding and those with minor bleeding. Hemostatic variables significantly improved over time during induction therapy. The recovery times of the PLT, PT, and Fbg values were significantly slower in patients with major bleeding than in those with minor bleeding. Specifically, the PLT level in patients with major bleeding was not similar to that in the minor bleeding group until after 4 weeks of treatment. Hemorrhages were the most common cause of induction death in this study. High-risk patients were more prone to serious clinical bleeding symptoms. Patients with major bleeding had more rapid proliferation characteristics and an increased incidence of FLT3-ITD

  5. An unusual cytogenetic rearrangement originating from two different abnormalities in chromosome 6 in a child with acute promyelocytic leukemia.

    Science.gov (United States)

    Matos, R R C; Mkrtchyan, H; Amaral, B A S; Liehr, T; de Souza, M T; Ney-Garcia, D R; Santos, N; Marques-Salles, T J; Ribeiro, R C; Figueiredo, A F; Silva, M L M

    2013-01-01

    Acute promyelocytic leukemia (APL) is usually associated with a favorable outcome, but about 10% of patients tend to relapse. The genetic hallmark of APL is a balanced translocation involving chromosomes 15 and 17, and the PML-RARa gene fusion is found in more than 90% of these cases. Other chromosomal abnormalities are commonly found in APL, but their clinical significance has yet to be determined. Here we report a case of childhood APL that was studied by conventional cytogenetics along with molecular cytogenetic techniques. The patient showed a complex karyotype with an unusual cytogenetic rearrangement originating from two different abnormalities in a single chromosome 6. Our case is an exceptional example of a cryptic cytogenetic anomaly in APL and underscores the importance of detailed genetic characterization. Copyright © 2013 S. Karger AG, Basel.

  6. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  7. Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.

    Directory of Open Access Journals (Sweden)

    Lorena L de Figueiredo-Pontes

    Full Text Available Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα expression in acute promyelocytic leukemia (APL impairs transforming growth factor beta (TGFβ signaling, leading to cell growth advantage. Halofuginone (HF, a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG. Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001 and induced apoptosis (P = 0.002 after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21 and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.

  8. Development of real-time quantitative polymerase chain reaction assays to track treatment response in retinoid resistant acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Jelena V Jovanovic

    2011-10-01

    Full Text Available Molecular detection of minimal residual disease (MRD has become established to assess remission status and guide therapy in patients with PML-RARA+ acute promyelocytic leukemia (APL. However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF-RARA and STAT5b-RARA. Despite their relative rarity (<1% of APL we identified 6 cases (PLZF-RARA, n=5; STAT5b-RARA, n=1, established the respective breakpoint junction regions and designed real-time quantitative polymerase chain reaction (RQ-PCR assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17-associated APL, affording assay sensitivities of ~1 in 104-105. Serial samples were available from 2 PLZF-RARA APL patients. One showed persistent PCR positivity, predicting subsequent relapse, and remains in CR2, ~11 years post-autograft. The other, achieved molecular remission (CRm with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b-RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RQ-PCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly-defined subsets of acute leukemia.

  9. Therapy-related myelodysplastic syndrome after successful treatment of acute promyelocytic leukemia: case report and literature review

    Directory of Open Access Journals (Sweden)

    Cîrstea Mihaela

    2017-04-01

    Full Text Available In the 2016 revision of the World Health Organization classification the term therapy-related myeloid neoplasia (t-MN defines a subgroup of acute myeloid leukemia (AML comprising patients who develop myelodysplastic syndrome (MDS-t or acute myeloid leukemia (AML-t after treatment with cytotoxic and/or radiation therapy for various malignancies or autoimmune disorders. We report the case of a 36 year old patient with t-MN (t-MDS after achieving complete remission (CR of a PML-RARA positive acute promyelocytic leukemia (APL at 32 months after diagnosis. Initially classified as low risk APL and treated according to the AIDA protocol - induction and 3 consolidation cycles - the patient achieved a complete molecular response in September 2013 and started maintenance therapy. On follow-up PML-RARA transcript remained negative. In January 2016 leukopenia and thrombocytopenia developed and a peripheral blood smear revealed hypogranular and agranular neutrophils. Immunophenotyping in the bone marrow aspirate identified undifferentiated blast cells that did not express cytoplasmic myeloperoxidase. The cytogenetic study showed normal karyotype. The molecular biology tests not identified PMLRARA transcript. A diagnosis of t-MDS (AREB-2 - WHO 2008 was established. Treatment of AML was started with 2 “3+7” regimens and 1 MEC cycle. Two months from diagnosis, while in CR, an allogeneic HSCT from an unrelated HLA compatible donor was performed after myeloablative regimen. An unfavorable clinical evolution was followed by death on day 9 after transplantation. The occurrence of t-MNs during CR of APL represents a particular problem in terms of follow-up and differential diagnosis of relapse and constitutes a dramatic complication for a disease with a favorable prognosis.

  10. [Atypical onset of therapy-related acute promyelocytic leukemia after combined modality therapy including (89)Sr for metastatic breast cancer].

    Science.gov (United States)

    Utsu, Yoshikazu; Aotsuka, Nobuyuki; Masuda, Shinichi; Matsuura, Yasuhiro; Wakita, Hisashi

    2013-08-01

    A 51-year-old woman diagnosed as having left breast cancer with axillary lymph node and liver metastases seven years earlier was seen in our office because of severe pancytopenia. She had received chemotherapy including several cycles of doxorubicin plus cyclophosphamide and docetaxel followed by hormone therapy containing leuprorelin and tamoxifen over four years. For management of bone pain due to metastasis, she had also undergone stereotaxic radiation therapy of the neck one and a half years earlier and unsealed internal radiation therapy with (89)Sr injection five months prior to the current presentation, Subsequently, myelosuppression progressively worsened and she finally required a blood transfusion. Although bone marrow examination showed severe hypoplasia, but neither blastic nor dysplastic, a test for PML-RARA fluorescence in situ hybridization was positive. After administration of all-trans retinoic acid, hematogenesis improved within three weeks. Neither disseminated intravascular coagulation nor retinoic acid syndrome was observed during the course of her illness. This is the first report describing acute promyelocytic leukemia after administration of (89)Sr, to our knowledge, and with an atypical onset and progression. As the number of cancer survivors increases due to improvements in medical intervention, clinicians must take more notice of special characteristics of therapy-related leukemia modified by previous treatments.

  11. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2016-01-01

    Full Text Available Background. Acute promyelocytic leukemia is characterized by t(15;17. This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA, a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

  12. Fournier's gangrene as first presentation of promyelocytic leukemia

    NARCIS (Netherlands)

    Faber, HJ; Girbes, ARJ; Daenen, S

    A 50-year-old male is described who presented with Fournier's gangrene as what is probably the first manifestation of a newly diagnosed acute myelogenous leukemia (AML), promyelocytic type or variant type M-3, according to the FAB classification. Despite aggressive fluid resuscitation, tuned

  13. Characteristics features and factors influencing early death in Acute promyelocytic leukemia; Experience from United Arab Emirates (UAE).

    Science.gov (United States)

    Hassan, Inaam Bashir; Zaabi, Mariam R Al; Alam, Arif; Hashim, Mohammed Jawad; Tallman, Martin S; Kristensen, Jorgen

    2017-07-01

    Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0.030), WBC count >20 × 10 9 /L (P = 0.010), the breakpoints other than bcr1 (P = 0.043) and fibrinogen level 10 × 10 9 /L and expression of HLA-DR (P = 0.018) or CD2 (P = 0.017) were significant predictors for differentiation syndrome (DS) which was found to be a predictor of ED (P = 0.002). Reducing the APL related ED rate in centers with limited resources is feasible provided early initiation of ATRA administration and early correction of coagulopathy in high-risk patients in addition to prompt treatment of DS. To our knowledge this is the first report from the Arabian Gulf describing ED in APL.

  14. [The First Switched Time of PML/RARα Fusion Gene in Patients with Acute Promyelocytic Leukemia and Its Clinical Significance].

    Science.gov (United States)

    Pu, Lian-Fang; Tao, Qian-Shan; Wang, Hui-Ping; Zhai, Zhi-Min; Xiong, Shu-Dao

    2015-12-01

    To investigate the first switched time of PML/RARα fusion gene in patients with acute promyelocytic leukemia (APL) and its clinical significance. sixty cases of newly diagnosed APL were enrolled in this study. They received standard remission induction, consolidation and maintenance treatments according to the clinical pathway for APL, and were followed up. During the same time the PML/RARα fusion gene mRNA expression of all cases was detected by multi-nested PCR. except for 3 death cases and 1 case failed to follow-up, the PML/RARα fusion genes in the remaining 56 cases were firstly found to be negative from 24 to 381 days respectively, the mean value of the first switched time was 131 ± 90 days. There was no statistically significant difference in age, sex and risk stratification between different groups. However, the cases with L-type PML/RARα gene had shorter time compared with the patients with S-type PML/RARα gene (P = 0.032); then, for the above-mentimed 56 cases, the follow-up duration ranged from 25-1979 days (median 946 days), long-term molecular remissions had been observed in most cases, but 1 case with the first switched time of 133 days unfortunately recurred to be positive and followed by clinical relapse. The PML/RARα fusion gene in newly diagnosed APL patients was first switched to be negative in about 4 months after treatment. The first switched time of PML/RARα fusion gene can objectively reflect the reduction of leukemia cells, and the differences among different subtypes of PML/RARα fusion gene may have some suggestions for the treatment, but without important significance for the evaluation of prognosis and recurrence for APL patients. In addition, minimal residual disease (MRD) can be dynamically monitored by detecting PML/RARα fusion gene, thus having an important clinical significance for analysis of APL recurrence.

  15. Comparative study of the efficacy of Wright-Giemsa stain and Liu's stain in the detection of Auer rods in acute promyelocytic leukemia.

    Science.gov (United States)

    Yue, Qing Fang; Xiong, Bei; Chen, Wan Xin; Liu, Xin Yue

    2014-07-01

    In view of the importance of Auer rods in the rapid diagnosis of acute promyelocytic leukemia, we compared the results of Wright-Giemsa stain and Liu's stain (a rapid and simple stain, which is also a kind of modified Romanowsky stain) in the detection of Auer rods. This study was based on 53 cases of acute promyelocytic leukemia. Two staining methods were respectively performed on the bone marrow smears of these cases, and presence of Auer rods as well as nuclear features, cytoplasmic features and the degree of granularity of the cytoplasm were compared in each case. Our results showed that the occurrence of Auer rods as well as faggots in leukemic promyelocytes were significantly higher under Liu's stain than under Wright-Giemsa stain. Significant differences also existed in the occurrence of hypergranular cells and cytoplasmic protrusions between smears stained with Liu's stain and Wright-Giemsa stain. Liu's stain is important for the rapid diagnosis of suspicious APL, especially in recognizing Auer rods. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. The impact of medical education and networking on the outcome of leukemia treatment in developing countries. The experience of International Consortium on Acute Promyelocytic Leukemia (IC-APL).

    Science.gov (United States)

    Rego, Eduardo M; Kim, Haesook T; Ruiz-Argüelles, Guillermo J; Uriarte, Maria del Rosario; Jacomo, Rafael H; Gutiérrez-Aguirre, Homero; Melo, Raul A M; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M; Chauffaille, Maria de Lourdes; Chiattone, Carlos; Martinez, Lem; Meillón, Luis A; Gómez-Almaguer, David; Kwaan, Hau; Garcés-Eisele, Javier; Gallagher, Robert; Niemeyer, Charlotte M; Lowenberg, Bob; Ribeiro, Raul; LoCoco, Francesco; Sanz, Miguel A

    2012-04-01

    Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay. The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced. The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%. The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries.

  17. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  18. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

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    Ola Khorshid

    2011-12-01

    Full Text Available The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate, toxicity and OS.

  19. Role of the polycomb repressive complex 2 in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Villa, Raffaella; Pasini, Diego; Gutierrez, Arantxa

    2007-01-01

    Epigenetic changes are common alterations in cancer cells. Here, we have investigated the role of Polycomb group proteins in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation induced by the leukemia-associated PML-RARalpha fusion protein. ...

  20. Trisomy 11 as an Additional Chromosome Alteration in a Child with Acute Promyelocytic Leukemia with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Elenice Ferreira Bastos

    2012-01-01

    Full Text Available The prognostic significance of the additional abnormalities to the t(15; 17 remains controversial. We report a case of promyelocytic leukemia (APL in a ten-year-old boy. Classical and molecular cytogenetic (FISH studies of a bone marrow sample obtained at diagnosis revealed the presence of trisomy of chromosome 11 as an additional chromosomal abnormality to the t(15; 17. The presence of the translocation t(15; 17, the cytogenetic marker of APL, is usually associated with good response to treatment with ATRA. In this case, although the patient had risk factors associated with good prognosis, he evolved and died quickly. So it seems that the presence of the trisomy 11 may be associated with disease progression and the poor outcome. To our knowledge, this is the first reported case of t(15; 17 associated with trisomy of chromosome 11 in a child with APL.

  1. Misfolded N-CoR is Linked to the Ectopic Reactivation of CD34/Flt3-Based Stem-Cell Phenotype in Promyelocytic and Monocytic Acute Myeloid Leukemia.

    Science.gov (United States)

    Nin, Dawn Sijin; Li, Feng; Visvanathan, Sridevi; Khan, Matiullah

    2015-01-01

    Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial

  2. [A successful case of tanshinone II A treatment for relapsed acute promyelocytic leukemia after maintainance therapy of all-trans retinoic acid and arsenic trioxide].

    Science.gov (United States)

    Yang, Lei; Gong, Yu-ping; Yang, Yi-ming; Luo, Shu

    2010-11-01

    To observe the effects of Tanshinone II A (Tan II A) on acute promyelocytic leukemia (APL) characterized by resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). A 21-year-old male patient with relapsed APL, who previously received the maintenance therapy with ATRA,ATO, 6-Mercaptopurine (6-MP) and Methotrexate (MTX) for 1 year, was given Tan II A 80 mg intravenously once a day, and the changes of hematological parameters and side effects of Tan II A were observed. The patient reached morphologically complete remission after using Tan II A intravenously for 54 days. During Tan II A treatment, obvious side effect was not observed. Tan II A treatment may be effective in relapsed APL cases with ATRA and ATO resistance.

  3. Diagnosis of disseminated candidiasis by fine needle aspiration of lymph node and by splenic imprint in a patient with acute promyelocytic leukemia.

    Science.gov (United States)

    Chao, T Y; Chang, J Y; Yu, C Y; Tsao, T Y

    1995-01-01

    Cytologic studies were done on fine needle aspirates of the lymph node and imprints of splenic biopsies from a patient with acute promyelocytic leukemia who was febrile while being treated with chemotherapy. Examination of the lymph node aspirates revealed pus and numerous pseudohyphae which were later identified as Candida tropicalis. When multiple nodular lesions were detected in the spleen by abdominal sonography and CT scan, needle biopsy of the spleen was done. Cytologic examination of touch imprints of the biopsy disclosed intracellular fungal blastospores. The patient was treated with and responded well to amphotericin B and 5-fluorocytosine. As a result of our experience with this patient we emphasize the importance of close incorporation of clinical information and diagnostic cytology. With such a cooperation, cytologic studies become a most useful method for diagnosis.

  4. Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia.

    Science.gov (United States)

    Xu, Wen; Li, Xiaoxia; Quan, Lina; Yao, Jiying; Mu, Guannan; Guo, Jingjie; Wang, Yitong

    2018-03-01

    Arsenic trioxide (ATO) exhibits substantial clinical efficacy in the treatment of acute promyelocytic leukemia (APL). Here, we investigated whether ATO exerts its efficacy by affecting regulatory T (Treg) cells. We determined whether ATO treatment influenced the amount and function of purified Treg cells. We also examined the effect of ATO treatment on Treg cells from APL patients. ATO treatment induced apoptosis in purified Treg cells and dampened the inhibition of effector T (Teff) cells proliferation and the secretion of cytokine by Treg cells. Treg cell levels in the peripheral blood and serum IL-10 levels were dramatically decreased in APL patients after single ATO treatment. In summary, our results show that ATO decreases the amount and inhibits the function of Treg cells, thereby enhancing Teff cell function and overall anti-tumor immunity.

  5. Y-chromosome loss as the sole karyotypic anomaly with 3'RARalpha submicroscopic deletion in a case of M3r subtype of acute promyelocytic leukemia.

    Science.gov (United States)

    Han, Yongsheng; Xue, Yongquan; Zhang, Jun; Pan, Jinlan; Wu, Yafang; Bai, Shuxiao

    2009-10-01

    Acute promyelocytic leukemia (APL) is characterized by the presence of a chromosomal rearrangement involving retinoic acid receptor alpha (RARalpha) gene generating the X-RARalpha fusion. We describe here a unique RARalpha gene rearrangement in a patient with M3r subtype of APL. Conventional cytogenetic analysis revealed Y-chromosome loss as the sole karyotypic anomaly. No X-RARalpha fusion was detected by fluorescence in situ hybridization (FISH) using PML/RARalpha dual-color dual-fusion translocation probe set, or RARalpha dual-color break apart rearrangement probe or reverse-transcription polymerase chain reaction (RT-PCR). However, FISH using RARalpha dual-color break apart rearrangement probe showed a deletion of the entire 3'-end of one allele of RARalpha gene. To our knowledge, this is the first documented APL with 3'RARalpha submicroscopic deletion which is not associated with X-RARalpha fusion. The molecular consequences of this anomaly remain to be elucidated.

  6. A Complicated Case of Acute Promyelocytic Leukemia in the Second Trimester of Pregnancy Successfully Treated with All-trans-Retinoic Acid

    Directory of Open Access Journals (Sweden)

    Kanika Agarwal

    2015-01-01

    Full Text Available A 40-year-old female at 26-week gestation was diagnosed with acute promyelocytic leukemia (APL after an abnormal prenatal lab workup showed pancytopenia. She was treated with all-trans-retinoic acid (ATRA, idarubicin, and dexamethasone. After day one of treatment, she developed differentiation syndrome, which was treated with dexamethasone. At 30-week gestation, she had preterm premature rupture of membranes and delivered by cesarean section because of the fetus’ breech presentation. Despite ATRA’s potential for teratogenicity, a viable infant was born without apparent anomalies. Postpartum, she underwent consolidation treatment with ATRA and arsenic trioxide (ATO. The patient continued ATRA therapy after delivery and is currently in remission.

  7. Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

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    Xi Zhang

    Full Text Available ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL accounts for 8% to 10% of cases of acute myeloid leukemia (AML. Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD, and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1 in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR. To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

  8. Detection of PML-retinoic acid receptor-alpha fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17).

    Science.gov (United States)

    Ikeda, K; Sasaki, K; Tasaka, T; Nagai, M; Kawanishi, K; Takahara, J; Irino, S

    1994-03-01

    Chromosome translocation t(15;17), the breakpoints of which are in the PML gene on chromosome 15 and retinoic acid receptor-alpha (RAR alpha) gene on chromosome 17, is specifically found in acute promyelocytic leukemia (APL). Clinically typical APL without t(15;17) and with the PML-RAR alpha fusion transcripts or rearrangements in PML and/or RAR alpha gene has been reported, suggesting submicroscopic changes at the molecular level without apparent t(15;17) or observation of normal metaphases. Trisomy 8 is common in APL as a secondary chromosomal abnormality in addition to t(15;17), as well as in acute myelogenous leukemia in general, but it is rare as a sole chromosomal anomaly in APL. PML-RAR alpha fusion transcript was detected in an APL case with trisomy 8 but without t(15;17), indicating that the leukemic cells lacked t(15;17) and still expressed the PML-RAR alpha fusion transcripts. This indicates that the same submicroscopic molecular changes as in APL with t(15;17) do occur in APL without t(15;17) and supports the use of molecular analysis for PML-RAR alpha fusion in APL.

  9. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    M.C. Azevedo

    2015-02-01

    Full Text Available In adults with non-promyelocytic acute myeloid leukemia (AML, high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69 received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27 received an intermediate-high-dose (<27 g/m2, and group 3 (n=35 received a very-high-dose (≥27 g/m2. Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients. The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21 and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96 than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

  10. The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein

    DEFF Research Database (Denmark)

    Alcalay, M; Tomassoni, L; Colombo, E

    1998-01-01

    PML is a nuclear protein with growth-suppressive properties originally identified in the context of the PML-retinoic acid receptor alpha (RAR alpha) fusion protein of acute promyelocytic leukemia. PML localizes within distinct nuclear structures, called nuclear bodies, which are disrupted...

  11. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

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

  12. [Adams-Stokes attack due to complete atrioventricular block in a patient with acute promyelocytic leukemia during remission induction therapy using all-trans retinoic acid].

    Science.gov (United States)

    Yamauchi, Takahiro; Arai, Hajime; Taga, Masahiro; Amaya, Naoki; Lee, Jong-Dae; Ueda, Takanori

    2005-03-01

    We describe a case of Adams-Stokes syncope due to complete atrioventricular block which occurred in a leukemic patient receiving all-trans retinoic acid (ATRA). Remission induction therapy was performed for a 46-year-old Japanese man with acute promyelocytic leukemia using ATRA (45 mg/m2), enocitabine (170 mg/m2, 5 days), and mitoxantrone (4 mg/m2, 3 days). On the 25th day of chemotherapy, syncope suddenly occurred. Electrocardiography revealed a complete atrioventricular block, and a temporary pacemaker was inserted on the following day. The block was persistent and the cardiac rhythm was dependent on the pacemaker. ATRA was discontinued on the 29th day because the arrhythmia was believed to be an adverse reaction to the ATRA regimen. The normal sinus rhythm was restored 15 days thereafter, and the patient eventually reached remission. He subsequently received 4 courses of consolidation therapy without any cardiovascular complications. Although ATRA sometimes induces arrhythmias, to the best of our knowledge this is the first report in the literature of such a critical ATRA-related arrhythmia.

  13. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Li Xiang-Xin

    2014-01-01

    Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

  14. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

    Science.gov (United States)

    Poiré, Xavier; Moser, Barry K; Gallagher, Robert E; Laumann, Kristina; Bloomfield, Clara D; Powell, Bayard L; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A; Tallman, Martin S; Appelbaum, Frederick R; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-07-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy.

  15. RAF-1/MEK/ERK pathway regulates ATRA-induced differentiation in acute promyelocytic leukemia cells through C/EBPβ, C/EBPε and PU.1.

    Science.gov (United States)

    Weng, Xiang-Qin; Sheng, Yan; Ge, Dong-Zheng; Wu, Jing; Shi, Lei; Cai, Xun

    2016-06-01

    MEK/ERK signal pathway was required for the differentiation of granulocytes, megakaryocytes and erythrocytes. Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. However, the upstream and downstream molecules of MEK/ERK signal pathway in this cell model remains to be elucidated. In this work, we showed that RAF-1 was activated and the blockade of RAF-1 activation attenuated MEK/ERK activation as well as ATRA-induced differentiation. ATRA-enhanced protein levels of C/EBPβ, C/EBPε and PU.1, which were required for differentiation in APL cells, were suppressed by the specific inhibitor of MEK. However, MEK inhibition had no effect on the degradation of PML-RARα fusion protein or the restoration of PML nuclear bodies by ATRA treatment. Taken together, our study suggested that RAF-1/MEK/ERK cascade was involved in ATRA-induced differentiation in APL cells through enhancing the protein level of C/EBPβ, C/EBPε and PU.1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Dasatinib synergizes with ATRA to trigger granulocytic differentiation in ATRA resistant acute promyelocytic leukemia cell lines via Lyn inhibition-mediated activation of RAF-1/MEK/ERK.

    Science.gov (United States)

    Ding, Ming; Weng, Xiang-Qin; Sheng, Yan; Wu, Jing; Liang, Cui; Cai, Xun

    2017-10-31

    All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In this study, dasatinib synergized with ATRA to trigger differentiation in ATRA-resistant APL cell lines. The combined treatment activated RAF-1, MEK and ERK as well as enhanced ATRA-promoted up-regulation of the protein level of PU.1, C/EBPβ and C/EBPε. U0126 (MEK specific inhibitor) and sorafenib tosylate (RAF-1 specific inhibitor) suppressed the combined treatment-induced differentiation, ERK phosphorylation and the up-regulation of C/EBPs and PU.1. Sorafenib tosylate also attenuated the MEK activity. However, the combined treatment did not enhance Ras activity and Ras inhibitor neither blocked MEK activation nor inhibited differentiation. Therefore, the combined treatment induced differentiation via Ras independent RAF-1/MEK/ERK. Earlier than RAF-1 activation, dasatinib suppressed Lyn activity, the predominant activated Src family kinase (SFK) and dephosphorylated RAF-1 at S259. Furthermore, SFK inhibitor, PP2 did suppress Lyn activity and mimicked the effect of dasatinib on ATRA-induced differentiation as well as decreased phosphorylation of RAF-1 at S259. Thus, it was suggested that Lyn inhibition might activate RAF-1 by the dephosphorylation of RAF at S259 and lead to differentiation. In conclusion, the combination of dasatinib and ATRA could overcome ATRA resistance through Lyn inhibition-mediated activation of RAF-1/MEK/ERK. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Coexistence of tetrasomy 8 and trisomy 8 in acute promyelocytic leukemia (AML-M3) with t(15;17)(q22;q12).

    Science.gov (United States)

    Wang, Hui-Ping; Li, Guo-Xia; Qiao, Zhen-Hua; Ren, Wen-Ying; Wang, Hong-Wei

    2004-08-01

    This study was purposed to characterize the first case of acute promyelocitic leukemia (AML-M(3a)) with t(15;17), trisomy 8 and tetrasomy 8, and explore its characteristics of morphology, cytogenetics, molecular biology, immunology and clinical features. Morphological changes of peripheral blood and bone marrow smears were observed under microscope. Chromosome specimen was prepared by 24 h short-term culture of bone marrow cell, RHG-banding technique was used for karyotypic analysis. PML-RARa fusion gene transcript was detected by nested-reverse transcription-polymerase chain reaction (nested RT-PCR). Interphase fluorescence in situ hybridization (FISH) using chromosome 8 centromere specific probe were carried out to detect abnormal numbers of chromosome 8. Immunophenotypic analysis was performed by flow cytometry. The results showed that peripheral blood smear revealed 65% promyelocyte, and bone marrow aspirate was hypercellular with 72.4% promyelocyte, moderately basophilic cytoplasm with numerous azurophilic granules. Karyotype analysis demonstrated 48, XY, +8, +8, t(15;17)(q22;q12) [16]/47, XY, +8, t(15;17)(q22;q12) [3]/46, XY, t(15;17)(q22;q12) [1]. RT-PCR assay revealed PML-RARa fusion gene transcript (+). FISH showed that the percentages of cells exhibiting 1, 2, 3, 4, 5, 6 green fluorescence signals were 0.5, 7, 19, 55, 18 and 0.5, respectively. This confirmed the presence of tetrasomy 8 and trisomy 8 and also revealed a low percentage of a pentasomy 8 clone. Immunophenotypes of the blasts displayed that CD13 (96.2%), CD33 (55.9%), CYMPO (93.5%) were positive. All the lymphoid markers tested were negative. The patient survival time was just 10 days. It is concluded that tetrasomy 8 is secondary cytogenetic event after t(15;17) in this case. It may be a consequence of clonal evolution of trisomy 8. t(15;17) AML-M(3) with tetrasomy 8 heralds a poor prognosis.

  18. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  19. Histone deacetylase inhibitors suppress IFN(alpha)-induced up-regulation of promyelocytic leukemia protein

    Czech Academy of Sciences Publication Activity Database

    Vlasáková, Jana; Nováková, Zora; Rossmeislová, Lenka; Kahle, Michal; Hozák, Pavel; Hodný, Zdeněk

    2007-01-01

    Roč. 109, č. 4 (2007), s. 1373-1380 ISSN 0006-4971 R&D Projects: GA ČR GA304/03/1210; GA AV ČR IAA500390501; GA ČR GEDYN/04/E002 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50520514 Keywords : Acute promyelocytic leukemia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.896, year: 2007

  20. Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARalpha.

    Science.gov (United States)

    Sukhai, Mahadeo A; Wu, Xuemei; Xuan, Yali; Zhang, Tong; Reis, Patricia P; Dubé, Karina; Rego, Eduardo M; Bhaumik, Mantu; Bailey, Denis J; Wells, Richard A; Kamel-Reid, Suzanne; Pandolfi, Pier Paolo

    2004-01-22

    Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in the bone marrow (BM), and by the presence of a reciprocal chromosomal translocation involving retinoic acid receptor alpha (RARalpha). To date, five RARalpha partner genes have been identified in APL. NuMA-RARalpha was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARalpha fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARalpha), two transgenic mouse lines were generated. Transgenic mice were observed to have a genetic myeloproliferation (increased granulopoiesis in BM) at an early age, and rapidly developed a myeloproliferative disease-like myeloid leukemia. This leukemia was morphologically and immunophenotypically indistinguishable from human APL, with a penetrance of 100%. The phenotype of transgenic mice was consistent with a blockade of neutrophil differentiation. NuMA-RARalpha is therefore sufficient for disease development in this APL model.

  1. Development and validation of a 3-Plex RT-qPCR assay for the simultaneous detection and quantitation of the three PML-RARa fusion transcripts in acute promyelocytic leukemia.

    Directory of Open Access Journals (Sweden)

    Zhanguo Chen

    Full Text Available Rapid diagnosis of acute promyelocytic leukemia (APL with promyelocytic leukemia-retinoic acid receptor alpha (PML-RARa contributes to a highly effective therapy with all-trans retinoic acid (ATRA. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR is a valuable tool to diagnose APL with PML-RARa. However, a single RT-qPCR analysis, which is laborious and costly, has to be performed in three reactions to determine whether one of the three PML-RARa transcripts is present and to quantify the involved transcript. This paper describes a novel TaqMan MGB probe-based 3-plex RT-qPCR assay in a single reaction to detect simultaneously the three PML-RARa transcripts. Specific primers and probe were designed, and the results were further normalized to the Abelson gene. The detection results for the serially diluted plasmid indicate that the analytical sensitivity was 10 copies per reaction for PML-RARa bcr1, bcr2, and bcr3. A relatively high sensitivity of 10-4 was achieved with this assay when analyzing the bcr1 transcripts obtained from the NB4 cell line. The reproducibility was satisfactory because the coefficients of variation of cycle threshold values were less than 3% for both inter- and intra-assays. After testing 319 newly diagnosed patients with leukemia (including 61 APL cases, the results of the 3-plex RT-qPCR assay completely agreed with the traditional methods used for the detection of PML-RARa. The quantitative results of the 3-plex RT-qPCR were highly correlated with the single RT-qPCR and showed similar assay sensitivity for 60 PML-RARa positive APL samples at diagnosis and 199 samples from 57 patients during follow-up. Interestingly, one PML-RARa bcr2 case at diagnosis with breakpoint at 1579, which was not detected by the single RT-q-PCR, was detected by the 3-plex RT-qPCR assay. The 3-plex RT-qPCR assay is a specific, sensitive, stable, and cost-effective method that can be used for the rapid diagnosis and

  2. New role for granulocyte colony-stimulating factor-induced extracellular signal-regulated kinase 1/2 in histone modification and retinoic acid receptor α recruitment to gene promoters: relevance to acute promyelocytic leukemia cell differentiation.

    Science.gov (United States)

    Cassinat, B; Zassadowski, F; Ferry, C; Llopis, L; Bruck, N; Lainey, E; Duong, V; Cras, A; Despouy, G; Chourbagi, O; Beinse, G; Fenaux, P; Rochette Egly, C; Chomienne, C

    2011-04-01

    The induction of the granulocytic differentiation of leukemic cells by all-trans retinoic acid (RA) has been a major breakthrough in terms of survival for acute promyelocytic leukemia (APL) patients. Here we highlight the synergism and the underlying novel mechanism between RA and the granulocyte colony-stimulating factor (G-CSF) to restore differentiation of RA-refractory APL blasts. First, we show that in RA-refractory APL cells (UF-1 cell line), PML-RA receptor alpha (RARα) is not released from target promoters in response to RA, resulting in the maintenance of chromatin repression. Consequently, RARα cannot be recruited, and the RA target genes are not activated. We then deciphered how the combination of G-CSF and RA successfully restored the activation of RA target genes to levels achieved in RA-sensitive APL cells. We demonstrate that G-CSF restores RARα recruitment to target gene promoters through the activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and the subsequent derepression of chromatin. Thus, combinatorial activation of cytokines and RARs potentiates transcriptional activity through epigenetic modifications induced by specific signaling pathways.

  3. Experience with four consecutive BFM-based protocols for treatment of childhood with non-promyelocytic acute myeloblastic leukemia in Argentina.

    Science.gov (United States)

    Felice, Maria S; Rossi, Jorge G; Alonso, Cristina N; Gallego, Marta S; Eberle, Silvia Eandi; Alfaro, Elizabeth M; Guitter, Myriam R; Bernasconi, Andrea R; Rubio, Patricia L; Coccé, Mariela C; Zubizarreta, Pedro A

    2016-09-01

    Childhood acute myeloid leukemia (AML) achieves event-free-survival (EFS) rates of ∼50%. Double induction phase has been introduced for improving these results. Four consecutive protocols for AML treatment were evaluated to assess the impact of the addition of a second induction course in our setting. From January 1990 to January 2014, 307 evaluable AML patients were accrued. They were classified into low-risk (LR) and high-risk (HR) according to cytogenetic/molecular findings and response on day 15. The first two studies administered one induction cycle while the latter two protocols administered double induction. Relapse was the most frequent event and early-deaths were reduced by 50% in the last protocol. Statistically significant differences were observed when comparing EFS in LR and HR groups. Patients from both risk-groups who received double induction achieved significantly better outcome. EFS improved in protocols with double induction and early-deaths rate was decreased. Cytogenetic/molecular features and early-response were confirmed as prognostic factors.

  4. High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study

    Directory of Open Access Journals (Sweden)

    Jae-Ho Yoon

    2017-01-01

    Full Text Available Abstract Wilms’ tumor gene 1 (WT1 expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen for WT1 monitoring. High WT1 expression (>120 copies/104 ABL1 after consolidation and at early period (3 months after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40 showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001 and inferior disease free survival (62.8 vs. 91.4%, P < 0.001. Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001 and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001 were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention. Trial registration Clinical Research Information Service (CRIS, KCT0002079

  5. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rafael Henriques Jácomo

    2008-02-01

    Full Text Available A leucemia promielocítica aguda (LPA é um modelo da aplicabilidade clínica dos conhecimentos moleculares fisiopatológicos. Caracteriza-se por alterações genéticas recorrentes que envolvem o gene do receptor alfa do ácido retinóico. A conseqüência é uma proteína com sensibilidade reduzida ao ligante, com bloqueio da diferenciação mielóide. Entretanto, doses suprafisiológicas do ácido all-trans-retinóico (ATRA são capazes de suplantar esta deficiência, e este é o princípio fundamental do tratamento da LPA, permitindo uma sobrevida livre de doença acima de 80% quando adequadamente tratada. Epidemiologicamente, difere dos demais subtipos de leucemia mielóide aguda por apresentar incidência predominante em adultos jovens e, aparentemente, maior incidência em países de colonização "latina". Contrastando com os excelentes resultados observados em países desenvolvidos, a mortalidade por LPA no Brasil ainda é alta, apesar da ampla disponibilidade das medicações no país.Acute promyelocytic leukemia (APL is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest. However, higher doses of all-trans-retinoic acid (ATRA are able to supersede this deficiency and this is the mainstay of APL treatment leading to over 80% disease free survival, when adequately treated. Epidemiologically, it differs from other acute myeloid leukemia due to a higher incidence in young adults and in countries of "Latin" colonization. Differing from excellent results observed in developed countries, APL mortality in Brazil is still high, despite the wide availability of drugs.

  6. The Promyelocytic Leukemia Zinc Finger Protein: Two Decades of Molecular Oncology

    International Nuclear Information System (INIS)

    Suliman, Bandar Ali; Xu, Dakang; Williams, Bryan Raymond George

    2012-01-01

    The promyelocytic leukemia zinc finger (PLZF) protein, also known as Zbtb16 or Zfp145, was first identified in a patient with acute promyelocytic leukemia, where a reciprocal chromosomal translocation t(11;17)(q23;q21) resulted in a fusion with the RARA gene encoding retinoic acid receptor alpha. The wild-type Zbtb16 gene encodes a transcription factor that belongs to the POK (POZ and Krüppel) family of transcriptional repressors. In addition to nine Krüppel-type sequence-specific zinc fingers, which make it a member of the Krüppel-like zinc finger protein family, the PLZF protein contains an N-terminal BTB/POZ domain and RD2 domain. PLZF has been shown to be involved in major developmental and biological processes, such as spermatogenesis, hind limb formation, hematopoiesis, and immune regulation. PLZF is localized mainly in the nucleus where it exerts its transcriptional repression function, and many post-translational modifications affect this ability and also have an impact on its cytoplasmic/nuclear dissociation. PLZF achieves its transcriptional regulation by binding to many secondary molecules to form large multi-protein complexes that bind to the regulatory elements in the promoter region of the target genes. These complexes are also capable of physically interacting with its target proteins. Recently, PLZF has become implicated in carcinogenesis as a tumor suppressor gene, since it regulates the cell cycle and apoptosis in many cell types. This review will examine the major advances in our knowledge of PLZF biological activities that augment its value as a therapeutic target, particularly in cancer and immunological diseases.

  7. Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds to low levels of arsenite.

    Science.gov (United States)

    Hirano, Seishiro; Watanabe, Takayuki; Kobayashi, Yayoi

    2013-12-15

    Inorganic arsenite (iAs(3+)) is a two-edged sword. iAs(3+) is a well-known human carcinogen; nevertheless, it has been used as a therapeutic drug for acute promyelocytic leukemia (APL), which is caused by a fusion protein comprising retinoic acid receptor-α and promyelocytic leukemia (PML). PML, a nuclear transcription factor, has a RING finger domain with densely positioned cysteine residues. To examine PML-modulated cellular responses to iAs(3+), CHO-K1 and HEK293 cells were each used to establish cell lines that expressed ectopic human PML. Overexpression of PML increased susceptibility to iAs(3+) in CHO-K1 cells, but not in HEK293 cells. Exposure of PML-transfected cells to iAs(3+) caused PML to change from a soluble form to less soluble forms, and this modification of PML was observable even with just 0.1 μM iAs(3+) (7.5 ppb). Western blot and immunofluorescent microscopic analyses revealed that the biochemical changes of PML were caused at least in part by conjugation with small ubiquitin-like modifier proteins (SUMOylation). A luciferase reporter gene was used to investigate whether modification of PML was caused by oxidative stress or activation of antioxidant response element (ARE) in CHO-K1 cells. Modification of PML protein occurred faster than activation of the ARE in response to iAs(3+), suggesting that PML was not modified as a consequence of oxidative stress-induced ARE activation. © 2013.

  8. Positive and negative predictive values of HLA-DR and CD34 in the diagnosis of acute promyelocytic leukemia and other types of acute myeloid leukemia with recurrent chromosomal translocations.

    Science.gov (United States)

    Promsuwicha, Orathai; Auewarakul, Chirayu U

    2009-12-01

    The predictive value of HLA-DR and CD34 in the diagnosis of four distinct genetic entities of acute myeloid leukemia (AML) is presently not established. We evaluated the positive and negative predictive values (PPV and NPV, respectively), sensitivity, specificity, and correlation coefficients of HLA-DR and CD34 in AML patients with t(15;17), t(8;21), inv(16), and abn(11q23). In AML with t(15;17) (n = 64), HLA-DR was expressed in 4.68% and CD34 was expressed in 15.62% and none of the cases expressed both HLA-DR and CD34. In AML with t(8;21) (n = 99), HLA-DR, CD34 or both antigens were expressed in the majority of cases (90.90%, 80.80%, and 79.79%, respectively). AML patients with inv(16) (n = 18) and abn(11q23) (n = 31) also highly expressed HLA-DR and CD34. Eight cases of t(8;21) and 1 case of abn(11q23) did not express either antigen. The highest correlation between CD34 and HLA-DR expression values was observed in cases with t(8;21) (r = 0.72) with the lowest correlation in inv(16) (r = 0.035). The PPV and NPV of HLA-DR-negativity plus CD34-negativity to predict t(15;17) was 85% and 100%, respectively, with 100% sensitivity and 92.74% specificity. The PPV and NPV of other myeloid markers such as CD117, MPO and CD11c to diagnose t(15;17) were much lower than those of HLA-DR and CD34. It was concluded that the absence of double negativity of HLA-DR and CD34 strongly predicts against t(15;17). Rare HLA-DR-positive/CD34-negative cases exist in patients with t(15;17) and 8% of t(8;21) cases expressed neither antigen. Further studies should determine whether HLA-DR-positive t(15;17) and HLA-DR-negative/CD34-negative t(8;21) represent a special entity associated with significant prognostic relevance.

  9. Restoration of CCAAT enhancer binding protein α P42 induces myeloid differentiation and overcomes all-trans retinoic acid resistance in human acute promyelocytic leukemia NB4-R1 cells

    Science.gov (United States)

    WANG, LIMENGMENG; XIAO, HAOWEN; ZHANG, XING; LIAO, WEICHAO; FU, SHAN; HUANG, HE

    2015-01-01

    All-trans retinoic acid (ATRA) is one of the first line agents in differentiation therapy for acute promyelocytic leukemia (APL). However, drug resistance is a major problem influencing the efficacy of ATRA. Identification of mechanisms of ATRA resistance are urgenly needed. In the present study, we found that expression of C/EBPα, an important transcription factor for myeloid differentiation, was significantly suppressed in ATRA resistant APL cell line NB4-R1 compared with ATRA sensitive NB4 cells. Moreover, two forms of C/EBPα were unequally suppressed in NB4-R1 cells. Suppression of the full-length form P42 was more pronounced than the truncated form P30. Inhibition of PI3K/Akt/mTOR pathway was also observed in NB4-R1 cells. Moreover, C/EBPα expression was reduced by PI3K inhibitor LY294002 and mTOR inhibitor RAD001 in NB4 cells, suggesting that inactivation of the PI3K/Akt/mTOR pathway was responsible for C/EBPα suppression in APL cells. We restored C/EBPα P42 and P30 by lentivirus vectors in NB4-R1 cells, respectively, and found C/EBPα P42, but not P30, could increase CD11b, CD14, G-CSFR and GM-CSFR expression, which indicated the occurrence of myeloid differentiation. Further upregulating of CD11b expression and differential morphological changes were found in NB4-R1 cells with restored C/EBPα P42 after ATRA treatment. However, CD11b expression and differential morphological changes could not be induced by ATRA in NB4-R1 cells infected with P30 expressing or control vector. Thus, we inferred that ATRA sensitivity of NB4-R1 cells was enhanced by restoration of C/EBPα P42. In addition, we used histone deacetylase inhibitor trichostatin (TSA) to restore C/EBPα expression in NB4-R1 cells. Similar enhancement of myeloid differentiation and cell growth arrest were detected. Together, the present study demonstrated that suppression of C/EBPα P42 induced by PI3K/Akt/mTOR inhibition impaired the differentiation and ATRA sensitivity of APL cells. Restoring C

  10. [Acute myeloid Leukemia].

    Science.gov (United States)

    Braess, Jan

    2016-11-01

    of between 8 and 10 months.The paradigm for genotype-specific therapy is acute promyelocytic leukemia (APL - or AML M3 in the former FAB classification). This entity used to be a problematic AML subgroup because of its frequent coagulation disturbances and potentially fatal bleeding problems. Today patients with APL can be treated with a chemotherapy free combination of ATRA - a differentiating agent - and Arsenic Trioxide - an apoptosis inducing agent. In patients with a leukocyte count 90 % can now be achieved. © Georg Thieme Verlag KG Stuttgart · New York.

  11. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Imilia Ismail

    2014-01-01

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

  12. Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds.

    Science.gov (United States)

    Sarma, Sailendra Nath; Kim, Youn-Jung; Ryu, Jae-Chun

    2010-05-27

    Benzene, toluene, o-xylene, ethylbenzene, trichloroethylene and dichloromethane are the most widely used volatile organic compounds (VOCs), and their toxic mechanisms are still undefined. This study analyzed the genome-wide expression profiles of human promyelocytic leukemia HL-60 cells exposed to VOCs using a 35-K whole human genome oligonucleotide microarray to ascertain potential biomarkers. Genes with a significantly increased expression levels (over 1.5-fold and p-values lines to VOC exposure.

  13. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  14. Differentiation of HL-60 promyelocytic leukemia cells monitored by flow cytometric measurement of nitro blue tetrazolium (NBT) reduction.

    Science.gov (United States)

    Blair, O C; Carbone, R; Sartorelli, A C

    1985-01-01

    Reduction of nitro blue tetrazolium (NBT) to insoluble blue formazan granules occurs during the stimulus-induced respiratory burst of mature granulocytes and is routinely used as an indicator of the extent of granulocytic differentiation of HL-60 acute promyelocytic leukemia cells. In the present study, the differentiation of HL-60 leukemia cells induced by dimethylsulfoxide (DMSO) or retinoic acid was monitored by flow cytometric (FCM) measurement of forward and 90 degree light scatter of NBT treated cells. Two-parameter correlated analysis permitted a distinction between cells with increased forward and decreased 90 degree light scatter (NBT-), and cells with decreased forward and increased 90 degree light scatter (NBT+). Fixation of NBT treated cells with 1% paraformaldehyde facilitated flow cytometric analysis, and allowed differences in NBT reduction to be quantitated. DMSO-induced cells expressed an all-or-none reduction of NBT to formazan, compared with retinoic acid treated cells that exhibited a graded response. Three parameter flow cytometric analysis of HL-60 leukemia cells stained with propidium iodide in combination with NBT allowed the determination of the cell cycle distribution of NBT-treated cells.

  15. Control of Hepatic Gluconeogenesis by the Promyelocytic Leukemia Zinc Finger Protein

    Science.gov (United States)

    Chen, Siyu; Qian, Jinchun; Shi, Xiaoli; Gao, Tingting; Liang, Tingming

    2014-01-01

    The promyelocytic leukemia zinc finger (PLZF) protein is involved in major biological processes including energy metabolism, although its role remains unknown. In this study, we demonstrated that hepatic PLZF expression was induced in fasted or diabetic mice. PLZF promoted gluconeogenic gene expression and hepatic glucose output, leading to hyperglycemia. In contrast, hepatic PLZF knockdown improved glucose homeostasis in db/db mice. Mechanistically, peroxisome proliferator-activated receptor γ coactivator 1α and the glucocorticoid receptor synergistically activated PLZF expression. We conclude that PLZF is a critical regulator of hepatic gluconeogenesis. PLZF manipulation may benefit the treatment of metabolic diseases associated with gluconeogenesis. PMID:25333514

  16. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

  17. Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Koschmieder, Steffen; Gelsing, Sandra

    2010-01-01

    Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperati...

  18. The effect of honey bee venom on the differentiation potency of D-alpha tocopheryl succinate (vitamin E on HL-60 promyelocytic leukemia cell line.

    Directory of Open Access Journals (Sweden)

    mohammad Nabiuni

    2014-01-01

    Full Text Available Background: Acute promyelocytic leukemia is the most malignant type of myeloid leukemia characterized by chromosomal translocation (15 and 17 and also blocking the cells in promyelocytic stage of differentiation into myeloid. Nowadays, differentiation therapy is used to treat leukemia. Previous studies indicate that vitamin E inhibits proliferation and also induces differentiation of HL-60 cell line towards monocyte. Since high concentrations of vitamin E to induce differentiation have many side effects, the search for alternative compounds is inevitable. Regarding anti- proliferative and anti-cancer effect of bee venom (BV, in this study the effect of BV on alpha tocopheryl succinate function in differentiation was examined. Materials and Methods: In this study cellular differentiation was tested by immunocytochemistry ,Wright-Giemsa staining and NBT reduction.Data were analyzed using one-way ANOVA test and Instate 3 software. Results: The results showed that BV in non-toxic concentrations can increase the differentiation potency of vitamin E on HL-60 cancer cell line. Conclusion: Non- toxic concentration of BV can increase differentiational effects of vitamin E and it is expected that BV can increases the differentiating potential of differentiator components in the future .

  19. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells.

    Science.gov (United States)

    Pilarski, Radosław; Poczekaj-Kostrzewska, Magdalena; Ciesiołka, Danuta; Szyfter, Krzysztof; Gulewicz, Krzysztof

    2007-01-01

    The woody Amazonian vine Uncaria tomentosa (cat's claw) has been recently more and more popular all over the world as an immunomodulatory, antiinflammatory and anti-cancer remedy. This study investigates anti-proliferative potency of several cat's claw preparations with different quantitative and qualitative alkaloid contents on HL-60 acute promyelocytic human cells by applying trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT). By standardization and statistical comparison of the obtained results pteropodine and isomitraphylline are indicated to be most suitable for standardization of medical cat's claw preparations.

  20. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was re...... from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL....

  1. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  2. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Directory of Open Access Journals (Sweden)

    Mohammed Al Huneini

    2013-05-01

    Full Text Available We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA for the treatment of acute promyelocytic leukemia (APL. Between October 2007 and March 2010, three males and one female (age range 19-35 years were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

  3. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Science.gov (United States)

    Al Huneini, Mohammed; Wasim, Fauzia; Al Farsi, Khalil; Al-Khabori, Murtadha; Al Kindi, Salam

    2013-01-01

    We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia (APL). Between October 2007 and March 2010, three males and one female (age range 19-35 years) were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA) as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted. PMID:23772289

  4. Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger.

    Science.gov (United States)

    Kim, Yeung-Hyen; Kumar, Ajay; Chang, Cheong-Hee; Pyaram, Kalyani

    2017-11-15

    Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological and pathological conditions as second messengers. ROS are essential for activation of T cells, but how ROS influence NKT cells is unknown. In the present study, we investigated the role of ROS in NKT cell function. We found that NKT cells, but not CD4 or CD8 T cells, have dramatically high ROS in the spleen and liver of mice but not in the thymus or adipose tissues. Accordingly, ROS-high NKT cells exhibited increased susceptibility and apoptotic cell death with oxidative stress. High ROS in the peripheral NKT cells were primarily produced by NADPH oxidases and not mitochondria. We observed that sorted ROS-high NKT cells were enriched in NKT1 and NKT17 cells, whereas NKT2 cells were dominant in ROS-low cells. Furthermore, treatment of NKT cells with antioxidants led to reduced frequencies of IFN-γ- and IL-17-expressing cells, indicating that ROS play a role in regulating the inflammatory function of NKT cells. The transcription factor promyelocytic leukemia zinc finger (PLZF) seemed to control the ROS levels. NKT cells from adipose tissues that do not express PLZF and those from PLZF haplodeficient mice have low ROS. Conversely, ROS were highly elevated in CD4 T cells from mice ectopically expressing PLZF. Thus, our findings demonstrate that PLZF controls ROS levels, which in turn governs the inflammatory function of NKT cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups.

    Science.gov (United States)

    Mandelli, F; Diverio, D; Avvisati, G; Luciano, A; Barbui, T; Bernasconi, C; Broccia, G; Cerri, R; Falda, M; Fioritoni, G; Leoni, F; Liso, V; Petti, M C; Rodeghiero, F; Saglio, G; Vegna, M L; Visani, G; Jehn, U; Willemze, R; Muus, P; Pelicci, P G; Biondi, A; Lo Coco, F

    1997-08-01

    Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

  6. Acute Lymphocytic Leukemia

    Science.gov (United States)

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

  7. Acute Myeloid Leukemia

    Science.gov (United States)

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

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

    Science.gov (United States)

    2018-02-28

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

  9. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia.

    Science.gov (United States)

    de Leeuw, David C; van den Ancker, Willemijn; Denkers, Fedor; de Menezes, Renée X; Westers, Theresia M; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Smit, Linda

    2013-04-15

    Classification of acute leukemia is based on the commitment of leukemic cells to the myeloid or the lymphoid lineage. However, a small percentage of acute leukemia cases lack straightforward immunophenotypical lineage commitment. These leukemias of ambiguous lineage represent a heterogeneous category of acute leukemia that cannot be classified as either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). The lack of clear classification of acute leukemias of ambiguous lineage as either AML or ALL is a hurdle in treatment choice for these patients. Here, we compared the microRNA (miRNA) expression profiles of 17 cases with acute leukemia of ambiguous lineage and 16 cases of AML, B-cell acute lymphoid leukemia (B-ALL), and T-cell acute lymphoid leukemia (T-ALL). We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to AML, B-ALL, or T-ALL. We show that by using only 5 of the most lineage-discriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL. Our results indicate the presence of a myeloid or lymphoid lineage-specific genotype, as reflected by miRNA expression, in these acute leukemias despite their ambiguous immunophenotype. miRNA-based classification of acute leukemia of ambiguous lineage might be of additional value in therapeutic decision making.

  10. Successful treatment of acute promyelocytic leukaemia without chemotherapy and blood transfusion

    DEFF Research Database (Denmark)

    Tøstesen, Michael; Østgård, Lene S G; Kjeldsen, Eigil

    2018-01-01

    Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year-old fe......-old female patient, who due to religious conviction refused supportive therapy with blood products. A treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was successful without the use of blood transfusions.......Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    ... Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) ... Coping Print en español Leucemia linfoblástica aguda About Leukemia Leukemia is a type of cancer that affects ...

  13. Promyelocytic Leukemia with No Retinoic Acid Receptor Alpha Abnormality but with RUNX1T1 Insertion to Chromosome 7q: A Classification and Management Dilemma

    Directory of Open Access Journals (Sweden)

    Kathleen Overholt

    2015-01-01

    Full Text Available A case of acute promyelocytic leukemia (APL with RUNX1T1 insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (RARA abnormality. In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH, and real-time polymerase chain reaction (RT-PCR showed no evidence of RARA rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of RUNX1T1. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of RARA rearrangement (by FISH and RT-PCR, present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML in future classifications.

  14. Acute leukemias of ambiguous origin.

    Science.gov (United States)

    Porwit, Anna; Béné, Marie C

    2015-09-01

    This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated. We emphasize that a comprehensive approach to immunophenotyping is required to accurately establish the diagnosis of MPAL. Flow cytometry immunophenotyping using a large panel of antibodies is needed as well as confirmatory immunohistochemical analysis and cytochemistry studies for myeloperoxidase and nonspecific esterase. We discuss technical issues in determining blast lineage and possible pitfalls in MPAL diagnosis. In particular, rare cases of B-acute lymphoblastic leukemia (B-ALL) can express myeloperoxidase but are otherwise consistent with B-ALL and should be treated as such. Last, we review the differential diagnosis between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation. There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough. Copyright© by the American Society for Clinical Pathology.

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

    Science.gov (United States)

    2018-02-22

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

  16. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

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

  18. Leucemia promielocítica aguda: caracterização de alterações cromossômicas por citogenética tradicional e molecular (FISH Acute promyelocytic leukemia: characterization of chromosome abnormalities by classical cytogenetics and FISH

    Directory of Open Access Journals (Sweden)

    Michele R. Sagrillo

    2005-06-01

    Full Text Available A leucemia promielocítica aguda (LPA corresponde a 10% -15% das leucemias mielóides agudas (LMA. Este tipo de leucemia (LMA-M3 de acordo com a classificação FAB está associado, em cerca de 90% dos casos, à translocação t(15;17(q22;q21, que resulta na fusão dos genes PML e RARalfa. A análise citogenética tradicional tem sido utilizada para confirmar o diagnóstico morfológico da LPA. Embora a t(15;17 não seja detectada em outros tipos de leucemia, podem ocorrer resultados "falso-negativos", decorrentes da análise de células que não pertencem ao clone neoplásico, da dificuldade de visualização da translocação ou, até mesmo, da existência de rearranjos crípticos que mascaram a translocação. Por outro lado, foram descritas alterações cromossômicas alternativas em pacientes com LPA e, nesses casos, o tratamento com ATRA não é eficaz. No período de julho de 1993 a dezembro de 2002 foram encaminhados para análise citogenética 47 casos com suspeita e/ou diagnóstico clínico-morfológico de LPA. Trinta e quatro pacientes (72,3% apresentaram a t(15;17, detectada pela citogenética tradicional e/ou molecular. Em seis destes pacientes foram observadas alterações cromossômicas adicionais ou rearranjos envolvendo um terceiro cromossomo. Em cinco (10% pacientes com características de LPA, a técnica de FISH não revelou a fusão PML/RARalfa, dado importante para a orientação do diagnóstico e da conduta terapêutica desses pacientes. O presente trabalho foi realizado com o objetivo de avaliar a importância da análise citogenética tradicional e molecular no diagnóstico de pacientes com LPA.Acute promyelocytic leukemia (APL accounts for 10 to 15% of acute myeloid leukemias (AML. This type of leukemia (AML-M3 according to the FAB classification is associated, in about 90% of the cases, with a t(15;17(q22;q21 translocation, resulting in the fusion of the PML and RARalpha genes. Traditional cytogenetic analysis has been

  19. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-17

    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); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  20. MANAGEMENT OF ACUTE PROMYELOCYTIC LEUKEMIA IN THE ELDERLY

    Directory of Open Access Journals (Sweden)

    Francesco Lococo

    2013-06-01

    Full Text Available Unlike other forms of AML, APL is less frequently diagnosed in the elderly and has a relatively favourable outcome. Elderly patients with APL seem at least as responsive to therapy as do younger patients, but rates of response and survival are lower in this age setting owing to a higher incidence of early deaths and deaths in remission when conventional treatment with ATRA and chemotherapy is used. Elderly APL patients are more likely to present with low-risk features compared with younger patients, and this may explain the relative low risk of relapse reported in several clinical studies. Alternative approaches, such as arsenic trioxide and gentuzumab ozogamicin have been tested with success in this setting and could replace in the near future frontline conventional chemotherapy and ATRA.

  1. Tailored Approaches to Induction Therapy for Acute Promyelocytic Leukemia.

    Science.gov (United States)

    DeAngelo, Daniel J

    2017-02-20

    The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

  2. Spotlight on the Diagnosis of Acute Promyelocytic Leukemia (AML ...

    African Journals Online (AJOL)

    QR-RT-PCR demonstrated bcr1 positivity in the 4 patients diagnosed by Karyotyping with t (15;17) and in the 8 patients can not diagnosed by Cytogenetic methods. Conclusion: Despite the fact that cytogenetics permit the identification of many chromosomal changes within a sample, FISH analysis is more sensitive when ...

  3. Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

    Science.gov (United States)

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

  4. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

    Science.gov (United States)

    Zwaan, C Michel; Kolb, Edward A; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S J M; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E S; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C; Rizzari, Carmelo; Rubnitz, Jeffrey E; Smith, Owen P; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M; Creutzig, Ursula; Kaspers, Gertjan J L

    2015-09-20

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. © 2015 by American Society of Clinical Oncology.

  5. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Zwaan, C. Michel; Kolb, Edward A.; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S.J.M.; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E.S.; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C.; Rizzari, Carmelo; Rubnitz, Jeffrey E.; Smith, Owen P.; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M.; Creutzig, Ursula; Kaspers, Gertjan J.L.

    2015-01-01

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML—supportive care—and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

  6. Rapidly progressing, fatal and acute promyelocytic leukaemia that initially manifested as a painful third molar: a case report

    Directory of Open Access Journals (Sweden)

    Suárez-Cuenca Juan A

    2009-11-01

    Full Text Available Abstract Introduction Acute promyelocytic leukaemia, an uncommon and devastating subtype of leukaemia, is highly prevalent in Latin American populations. The disease may be detected by a dentist since oral signs are often the initial manifestation. However, despite several cases describing oral manifestations of acute promyelocytic leukaemia and genetic analysis, reports of acute promyelocytic leukaemia in Hispanic populations are scarce. The identification of third molar pain as an initial clinical manifestation is also uncommon. This is the first known case involving these particular features. Case presentation A 24-year-old Latin American man without relevant antecedents consulted a dentist for pain in his third molar. After two dental extractions, the patient experienced increased pain, poor healing, jaw enlargement and bleeding. A physical examination later revealed that the patient had pallor, jaw enlargement, ecchymoses and gingival haemorrhage. Laboratory findings showed pancytopaenia, delayed coagulation times, hypoalbuminaemia and elevated lactate dehydrogenase. Splenomegaly was detected on ultrasonography. Peripheral blood and bone marrow analyses revealed a hypercellular infiltrate of atypical promyelocytic cells. Cytogenetic analysis showing genetic translocation t(15;17 further confirmed acute promyelocytic leukaemia. Despite early chemotherapy, the patient died within one week due to intracranial bleeding secondary to disseminated intravascular coagulation. Conclusion The description of this unusual presentation of acute promyelocytic leukaemia, the diagnostic difficulties and the fatal outcome are particularly directed toward dental surgery practitioners to emphasise the importance of clinical assessment and preoperative evaluation as a minimal clinically-oriented routine. This case may also be of particular interest to haematologists, since the patient's cytogenetic analysis, clinical course and therapeutic response are well

  7. Genomic Characterization of Acute Leukemias

    Science.gov (United States)

    Chiaretti, Sabina; Gianfelici, Valentina; Ceglie, Giulia; Foà, Robin

    2014-01-01

    Over the past two decades, hematologic malignancies have been extensively evaluated due to the introduction of powerful technologies, such as conventional karyotyping, FISH analysis, gene and microRNA expression profiling, array comparative genomic hybridization and SNP arrays, and next-generation sequencing (including whole-exome sequencing and RNA-seq). These analyses have allowed for the refinement of the mechanisms underlying the leukemic transformation in several oncohematologic disorders and, more importantly, they have permitted the definition of novel prognostic algorithms aimed at stratifying patients at the onset of disease and, consequently, treating them in the most appropriate manner. Furthermore, the identification of specific molecular markers is opening the door to targeted and personalized medicine. The most important findings on novel acquisitions in the context of acute lymphoblastic leukemia of both B and T lineage and de novo acute myeloid leukemia are described in this review. PMID:24968698

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

    Science.gov (United States)

    Chung, Clement; Ma, Hilary

    2017-09-01

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

  9. In vitro radiosensitivity of human leukemia cell lines

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Greenberger, J.S.; Schmidt, A.; Karpas, A.; Moloney, W.C.; Little, J.B.

    1981-01-01

    The in vitro radiobiologic survival values (anti n, D 0 ) of four tumor lines derived from human hematopoietic tumors were studied. These cell lines were HL60 promyelocytic leukemia; K562 erythroleukemia; 45 acute lymphocytic leukemia; and 176 acute monomyelogenous leukemia. More cell lines must be examined before the exact relationship between in vitro radiosensitivity and clinical radiocurability is firmly established

  10. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    Science.gov (United States)

    ... normal acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer ...

  11. Genetics Home Reference: core binding factor acute myeloid leukemia

    Science.gov (United States)

    ... acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  12. Epidemiology of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Pendergrass, T.W.

    1985-01-01

    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

  13. Extramedullary leukemia in children with acute myeloid leukemia

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...

  14. Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells

    Directory of Open Access Journals (Sweden)

    Zheng Li

    2017-03-01

    Full Text Available Despite the apparent clinical benefits of high-dose cytarabine (Ara-C over lower dose Ara-C in acute myeloid leukemia (AML therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60 after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK and subsequently Forkhead Box, class O (FoxO, to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML.

  15. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. An unusual case of acute leukemia.

    Science.gov (United States)

    Fleury, Carole; Passet, Marie; Settegrana, Catherine; Simon, Laurence; Chapiro, Elise; Trinquand, Amélie; Safra Zaghouani, Ines; Uzunov, Madalina; Le Garff-Tavernier, Magali; Armand, Marine; Costopoulos, Myrto

    2017-06-01

    We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified partial rearrangements in immunoglobulin and TCR genes, allowing the monitoring of minimal residual disease. This observation highlights the difficulty to classify some atypical cases of acute leukemias. It emphasizes on the complementarity of cytomorphology, immunophenotyping by flow cytometry and molecular techniques in order to promptly characterize and treat these leukemias.

  17. Epigenetic Regulation of Hematopoiesis and Acute Leukemia

    NARCIS (Netherlands)

    D.G. Valerio (Daria)

    2017-01-01

    markdownabstractIn this thesis we have explored chromatin regulation in acute leukemia and normal hematopoiesis. In doing so, we have focused on the H3K4 methyltransferase MLL1 and the H4K16 acetyltransferase MOF. MLL- and NUP98-translocations are quite common in acute leukemia and even more

  18. acute leukemias immunophenotypes at agakhan university hospital ...

    African Journals Online (AJOL)

    2013-02-01

    Feb 1, 2013 ... specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics ... Conclusion: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these ..... AML-M2 in both pediatric and adult population in. India(15). The proportion of ...

  19. [Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

    Science.gov (United States)

    Schlenk, R F; Döhner, K; Döhner, H

    2013-02-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

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

    Science.gov (United States)

    2017-03-27

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

  1. Promyelocytic Sarcoma of the Spine: A Case Report and Review of the Literature

    OpenAIRE

    Pacilli, Leonardo; Lo Coco, Francesco; Ramadan, Safaa Mahmoud; Giann?, Laura; Pingi, Alberto; Remotti, Daniele; Majolino, Ignazio

    2010-01-01

    Myeloid sarcoma (MS, previously named granulocytic sarcoma or chloroma) is a rare extramedullary tumour of immature myeloid cells. It can be present before, concurrently with, or after the diagnosis of acute myeloid leukemia. MS is extremely uncommon in acute promyelocytic leukemia (APL). In the case described here, MS was the sole site of APL relapse and the cause of spinal cord compression. The patient presented with neurologic symptoms due to a paravertebral mass of MS after 7 years of com...

  2. Acute Myelogenous Leukemia Mimicking Fulminant Periorbital Cellulitis

    Directory of Open Access Journals (Sweden)

    Abbas Bagheri

    2013-01-01

    Full Text Available Purpose: To report a patient who was referred for orbital cellulitis but was finally diagnosed with acute leukemia. Case Report: A 17-year-old boy presented with fever, periorbital erythema and swelling mimicking periorbital cellulitis. He underwent empiric antibiotic therapy. Complete blood counts revealed leukocytosis with a predominance of immature blast cells. Bone marrow aspiration confirmed the diagnosis of acute myelogenous leukemia. Chemotherapy was initiated resulting in resolution of signs and symptoms. Conclusion: Acute leukemia may mimic periorbital cellulitis and must be considered in the differential diagnosis.

  3. Multiplex fusion gene testing in pediatric acute myeloid leukemia.

    Science.gov (United States)

    Iijima-Yamashita, Yuka; Matsuo, Hidemasa; Yamada, Miho; Deguchi, Takao; Kiyokawa, Nobutaka; Shimada, Akira; Tawa, Akio; Takahashi, Hiroyuki; Tomizawa, Daisuke; Taga, Takashi; Kinoshita, Akitoshi; Adachi, Souichi; Horibe, Keizo

    2018-01-01

    Gene abnormalities, particularly chromosome rearrangements generating gene fusion, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification, but the results are not always consistent with those of reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and from acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation. Multiplex quantitative RT-PCR was performed to detect eight important fusion genes: AML1(RUNX1)-ETO(RUNX1T1), CBFB-MYH11, MLL(KMT2A)-AF9(MLLT3), MLL-ELL, MLL-AF6(MLLT4), FUS(TLS)-ERG, NUP98-HOXA9, and PML-RARA. Fusion genes were detected in 207 (46.2%) of the 448 AML-05 patient samples. After exclusion of two samples with PML-RARA, no chromosomal abnormalities were identified on karyotyping in 19 of 205 patients (9.3%) positive for fusion genes on RT-PCR. Fusion genes were confirmed on fluorescence in situ hybridization (FISH) in 11 of these 19 patients. In contrast, fusion genes were detected in 37 of 39 patients (94.9%) from the AML-P05 study, and 33 of these results were consistent with the karyotyping. There were discrepancies in four patients (10.8%), three with normal karyotypes and one in whom karyotyping was not possible. All four of these patients were PML-RARA positive on FISH. Multiplex quantitative RT-PCR-based fusion gene screening may be effective for diagnosis of pediatric AML. © 2017 Japan Pediatric Society.

  4. 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

    Science.gov (United States)

    2018-03-05

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  5. HLA-DR(negative), CD34(negative) hypergranular acute myeloid leukemia with trisomy 6 and del(5)(q22q33): case report and review of the literature.

    Science.gov (United States)

    Argiropoulos, Bob; Clifford, Brian; Crocker, Susan; Sinclair-Bourque, Elizabeth; McCready, Elizabeth; McGowan-Jordan, Jean; Johnston, Donna L; Padmore, Ruth

    2011-10-01

    We report a unique pediatric case of hypergranular acute myeloid leukemia with myelodysplasia-related changes. The patient presented with moderate leukocytosis with neutrophilia with left-shift maturation and dysplasia, anemia, and multiple sclerotic bone lesions. The bone marrow was hypercellular with a predominance of myeloblast cells and/or abnormal promyelocytes with hypergranular cytoplasm. Flow cytometric immunophenotyping showed that the leukemic cells were positive for CD13, CD33, and myeloperoxidase, and negative for HLA-DR and CD34. Morphology and immunophenotyping were highly suggestive of acute promyelocytic leukemia. The classic t(15;17) or other RARα rearrangements were not detected by cytogenetic or molecular assays, ruling out acute promyelocytic leukemia. Standard cytogenetic analysis showed that the karyotype of the predominant clone was 47,XY,+6 with evidence of clonal evolution to 47,XY,+6,del(5)(q22q33). A literature and database review showed that trisomy 6 is a rare occurrence in hematological malignancies and, to our knowledge, has never been reported in association with del(5)(q22q33) in a child presenting with hypergranular acute myeloid leukemia with myelodysplasia-related changes. We present a current review of the literature and summarize the clinical features of 57 cases of trisomy 6 as the primary chromosomal abnormality in hematological disease.

  6. Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis.

    Science.gov (United States)

    Manikam, Shiamala D; Manikam, Shiamala T; Stanslas, Johnson

    2009-01-01

    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2). In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 microM) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 microM). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2xIC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia.

  7. Ablation of Promyelocytic Leukemia Protein (PML) Re-patterns Energy Balance and Protects Mice from Obesity Induced by a Western Diet*

    Science.gov (United States)

    Cheng, Xiwen; Guo, Shuang; Liu, Yu; Chu, Hao; Hakimi, Parvin; Berger, Nathan A.; Hanson, Richard W.; Kao, Hung-Ying

    2013-01-01

    The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Mice with a deletion in the gene for PML (KO mice) exhibit altered gene expression in liver, adipose tissue, and skeletal muscle, an accelerated rate of fatty acid metabolism, abnormal glucose metabolism, constitutive AMP-activating kinase (AMPK) activation, and insulin resistance in skeletal muscle. Last, an increased rate of energy expenditure protects PML KO mice from the effects of obesity induced by a Western diet. Collectively, our study uncovers a previously unappreciated role of PML in the regulation of metabolism and energy balance in mice. PMID:23986437

  8. Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries

    DEFF Research Database (Denmark)

    Wennström, Lovisa; Edslev, Pernille Wendtland; Abrahamsson, Jonas

    2016-01-01

    BACKGROUND: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. PROCEDURE: We investigated disease characteristics and outcome...... countries. RESULTS: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients...... for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic...

  9. Alterations in polyamine levels induced by phorbol diesters and other agents that promote differentiation in human promyelocytic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Weeks, C.; Herrmann, A.; Callaham, M.; Slaga, T.

    1981-02-01

    Polyamine levels were evaluated in human HL-60 promyelocytic leukemia cells after treatment with inducers of terminal differentiation. Differentiation in these cells was determined by increases in the percentage of morphologically mature cells and in lysozyme activity. Treatment of the HL-60 cells with phorbol 12-myristate-13-acetate (PMA), phorbol 12,13-didecanoate or other inducers of terminal differentiation such as dimethylsulfoxide and retinoic acid resulted in increased levels of putrescine. However, no increase in putrescine could be detected after PMA treatment of a HL-60 cell variant that exhibited a decreased susceptibility to PMA-induced terminal differentiation. Similarly, no increase in putrescine was observed with two nontumor-promoters (phorbol 12,13-diacetate and 4-O-methyl-PMA) or with anthralin, a non-phorbol tumor promoter. In addition to enhancing putrescine levels, PMA also increased the amount of spermidine and decreased the amount of spermine. The increase in putrescine and spermidine preceded the expression of the various differentiation markers. Unlike the changes observed in the polyamine levels after PMA treatment, the activities of ornithine and S-adenosylmethionine decarboxylases, which are polyamine biosynthetic enzymes, did not significantly change. ..cap alpha..-Methylornithine and ..cap alpha..-difluoromethylornithine and methylglyoxal bis(guanylhydrazone), which are inhibitors of the polyamine biosynthetic enzymes, did not affect differentiation in control or PMA-treated cells. Because of these observations, we suggest that the change in polyamine levels involve biochemical pathways other than the known biosynthetic ones. By-products of these pathways may perhaps be the controlling factors involved in the induction of terminal differentiation in the HL-60 and other cell types as well.

  10. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    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.

  11. Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation: sumoylation of PML and phospho-switch control of its SUMO binding domain dissected in living cells.

    Science.gov (United States)

    Percherancier, Yann; Germain-Desprez, Delphine; Galisson, Frédéric; Mascle, Xavier H; Dianoux, Laurent; Estephan, Patricia; Chelbi-Alix, Mounira K; Aubry, Muriel

    2009-06-12

    Promyelocytic leukemia protein (PML) is a tumor suppressor acting as the organizer of subnuclear structures called PML nuclear bodies (NBs). Both covalent modification of PML by the small ubiquitin-like modifier (SUMO) and non-covalent binding of SUMO to the PML SUMO binding domain (SBD) are necessary for PML NB formation and maturation. PML sumoylation and proteasome-dependent degradation induced by the E3 ubiquitin ligase, RNF4, are enhanced by the acute promyelocytic leukemia therapeutic agent, arsenic trioxide (As2O3). Here, we established a novel bioluminescence resonance energy transfer (BRET) assay to dissect and monitor PML/SUMO interactions dynamically in living cells upon addition of therapeutic agents. Using this sensitive and quantitative SUMO BRET assay that distinguishes PML sumoylation from SBD-mediated PML/SUMO non-covalent interactions, we probed the respective roles of covalent and non-covalent PML/SUMO interactions in PML degradation and interaction with RNF4. We found that, although dispensable for As2O3-enhanced PML sumoylation and RNF4 interaction, PML SBD core sequence was required for As2O3- and RNF4-induced PML degradation. As confirmed with a phosphomimetic mutant, phosphorylation of a stretch of serine residues, contained within PML SBD was needed for PML interaction with SUMO-modified protein partners and thus for NB maturation. However, mutation of these serine residues did not impair As2O3- and RNF4-induced PML degradation, contrasting with the known role of these phosphoserine residues for casein kinase 2-promoted PML degradation. Altogether, these data suggest a model whereby sumoylation- and SBD-dependent PML oligomerization within NBs is sufficient for RNF4-mediated PML degradation and does not require the phosphorylation-dependent association of PML with other sumoylated partners.

  12. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    Science.gov (United States)

    2018-03-02

    Adult Acute Myeloid Leukemia in Remission; Acute Biphenotypic Leukemia; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Acute Myeloid Leukemia; Adult Acute Lymphoblastic Leukemia; Interleukin-3 Receptor Subunit Alpha Positive; Minimal Residual Disease; Refractory Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). Copyright © 2016. Published by Elsevier Inc.

  14. Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure.

    Science.gov (United States)

    Firkin, Frank; Roncolato, Fernando; Ho, Wai Khoon

    2015-10-01

    To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-11-01

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

  16. Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte.

    Science.gov (United States)

    Lee, Kyung-Won; Kim, Hyoung Ja; Lee, Yong Sup; Park, Hee-Jun; Choi, Jong-Won; Ha, Joohun; Lee, Kyung-Tae

    2007-09-01

    We investigated the in vitro effects of acteoside on the proliferation, cell cycle regulation and differentiation of HL-60 human promyelocytic leukemia cells. Acteoside inhibited the proliferation of HL-60 cells in a concentration- and time-dependent manner with an IC50, approximately 30 microM. DNA flow cytometric analysis indicated that acteoside blocked cell cycle progression at the G1 phase in HL-60 human promyelocytic leukemia cells. Among the G1 phase cell cycle-related proteins, the levels of cyclin-dependent protein kinase (CDK)2, CDK6, cyclin D1, cyclin D2, cyclin D3 and cyclin E were reduced by acteoside, whereas the steady-state level of CDK4 was unaffected. The protein and mRNA levels of CDK inhibitors (cyclin-dependent kinase inhibitors), such as p21(CIP1/WAF1) and p27(KIP1), were gradually increased after acteoside treatment in a time-dependent manner. In addition, acteoside markedly enhanced the binding of p21(CIP1/WAF1) and p27(KIP1) to CDK4 and CDK6, resulting in the reduction of CDK2, CDK4 and CDK6 activities. Moreover, the hypophosphorylated form of retinoblastoma increased, leading to the enhanced binding of protein retinoblastoma (pRb) and E2F1. Our results further suggest that acteoside is a potent inducer of differentiation of HL-60 cells based on biochemical activities and the expression level of CD14 cell surface antigen. In conclusion, the onset of acteoside-induced G1 arrest of HL-60 cells prior to the differentiation appears to be tightly linked to up-regulation of the p21(CIP1/WAF1) and p27(KIP1) levels and decreases in the CDK2, CDK4 and CDK6 activities. These findings, for the first time, reveal the mechanism underlying the anti-proliferative effect of acteoside on human promyelocytic HL-60 cells.

  17. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    Science.gov (United States)

    2018-01-24

    Acute Undifferentiated Leukemia; 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); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Benzene and childhood acute leukemia in Oklahoma.

    Science.gov (United States)

    Janitz, Amanda E; Campbell, Janis E; Magzamen, Sheryl; Pate, Anne; Stoner, Julie A; Peck, Jennifer D

    2017-10-01

    Although childhood cancer is a leading cause of childhood mortality in the US, evidence regarding the etiology is lacking. The goal of this study was to evaluate the association between benzene, a known carcinogen, and childhood acute leukemia. We conducted a case-control study including cases diagnosed with acute leukemia between 1997 and 2012 (n = 307) from the Oklahoma Central Cancer Registry and controls matched on week of birth from birth certificates (n = 1013). We used conditional logistic regression to evaluate the association between benzene, measured with the 2005 National-Scale Air Toxics Assessment (NATA) at census tract of the birth residence, and childhood acute leukemia. We observed no differences in benzene exposure overall between cases and controls. However, when stratified by year of birth, cases born from 2005 to 2010 had a three-fold increased unadjusted odds of elevated exposure compared to controls born in this same time period (4th Quartile OR: 3.53, 95% CI: 1.35, 9.27). Furthermore, the estimates for children with acute myeloid leukemia (AML) were stronger than those with acute lymphoid leukemia, though not statistically significant. While we did not observe an association between benzene and childhood leukemia overall, our results suggest that acute leukemia is associated with increased benzene exposure among more recent births, and children with AML may have increased benzene exposure at birth. Using the NATA estimates allowed us to assess a specific pollutant at the census tract level, providing an advantage over monitor or point source data. Our study, however, cannot rule out the possibility that benzene may be a marker of other traffic-related exposures and temporal misclassification may explain the lack of an association among earlier births. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Thrombosis in adult patients with acute leukemia.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Del Principe, Domenico; Venditti, Adriano

    2017-11-01

    Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA. Furthermore, leukemic blasts can activate the procoagulant population of platelets, which initiate and amplify coagulation, causing thrombosis. In addition to factors produced by acute leukemia itself, others concur to trigger thrombosis. Some drugs, infections and insertion of central venous catheter have been described to increase risk of thrombosis in patients with acute leukemia. Thrombosis represents a serious complication in patients affected by myeloid and lymphoid acute leukemia. A proper knowledge of its pathophysiology and of the predisposing risk factors may allow to implement strategies of prevention. Improving prevention of thrombosis appears a major goal in patients whose frequent conditions of thrombocytopenia impede an adequate delivery of anticoagulant therapy.

  20. Nucleophosmin 1 expression in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Mohammad Davoudi

    2015-09-01

    Full Text Available Nucleophosmin1 is a multifunctional protein that shuttles between nucleus and cytoplasm in some subtypes of acute myeloid leukemias. Mutated Nucleophosmin1 expresses aberrantly in the cytoplasm of the cell and transports from nucleolus to the cytoplasm. It is diagnosed by immunohistochemical techniques, flow cytometry assay and mutational analysis.The aim of this study is to evaluate the effects of Nucleophosmin1 mutation on the clinical presentations, prognosis, diagnosis and the treatment of acute myeloid leukemia. Thirteen articles were extracted from PubMed, Google scholar and Scopus in which the Nucleophosmin1 mutation correlated with gingival hyperplasia, high white blood cell count, lymphadenopathy, high platelet count and other signs and symptoms of myelomonocytic and monocytic acute myeloid leukemias. This mutation is a provisional entity in the classification of acute myeloid leukemia, which influences on the prognosis, clinical course and the treatment of some subtypes of acute myeloid leukemias. Nucleophosmin1 mutation has favorable prognostic value in the absence of other concomitant mutations.

  1. 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

    Science.gov (United States)

    2018-03-19

    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

  2. FISH Detection of PML-RARA Fusion in ins(15;17 Acute Promyelocytic Leukaemia Depends on Probe Size

    Directory of Open Access Journals (Sweden)

    Lynda J. Campbell

    2013-01-01

    Full Text Available The diagnosis of acute promyelocytic leukaemia (APL is usually confirmed by cytogenetics showing the characteristic t(15;17, but a minority of patients have a masked PML/RARA fusion. We report ten patients with APL and no evidence of the t(15;17, in whom the insertion of RARA into PML could not be demonstrated by initial FISH studies using a standard dual fusion probe but was readily identified using smaller probes. Given the need for rapid diagnosis of APL, it is important to be aware of the false negative rate for large PML/RARA FISH probes in the setting of masked rearrangements.

  3. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Xueqing Jiang

    Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

  4. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    Science.gov (United States)

    2018-03-26

    HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

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

    Science.gov (United States)

    2013-06-04

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

  6. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

    Han Li-na, [No Value; Zhou Jin, [No Value; Schuringa, Jan Jacob; Vellenga, Edo

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials. Data sources The data in this article were collected from PubMed database with relevant

  7. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    OpenAIRE

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2014-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene.

  8. CYTOGENETIC ANALYSIS IN SLOVENIAN ACUTE LEUKEMIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Helena Podgornik

    2008-04-01

    Using molecular cytogenetic and genetic methods a possibility that some of chromosomalchanges were overlooked was considerably minimized. On the basis of the analyzed datawe can be confident that the cytogenetic diagnostic approach in our acute leukemia patients is in accordance with international guidelines

  9. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Having a child with cancer can make you feel very alone. In a cancer support group, you can find people who are going ... Updated July 28, 2016. National Cancer Institute. www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq . Accessed August 3, 2016. Wei ...

  10. The MLL recombinome of acute leukemias in 2013

    DEFF Research Database (Denmark)

    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 ...

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

    Science.gov (United States)

    2016-05-13

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

  12. Clinico-pathological profile of acute promyelocytic leukaemia at Al-Amal Oncology-Haematology Centre, Qatar.

    Science.gov (United States)

    Ibrahim, F A; Yassin, M A; El-Ayoubi, H R; Alhiji, I A; Albinali, A S; Almansour, S M; Qafoud, F M

    2010-09-01

    This cases series describes the profile of adult patients with acute promyelocytic leukaemia (APt) at a referral hospital in Qatar. Of 34 acute myeloid leukaemia (AML) cases diagnosed, 11(32%) were classified as APt. Disseminated intravascular coagulation was common at presentation (91%). Severe thrombocytopenia was seen in 73%, leukocytosis in 55% and severe anaemia in 45%. Only 2 patients were of the classic hypergranular type. In the remaining 9 patients, 3 morphological subtypes were recognized: microgranular variant (6 patients), hyperbasophilic (2 patients) and regular nuclear outline M3r (1 patient). Translocation t(15;17) was detected in 63% of cases. APL constitutes a high proportion of AML cases in Qatar, with considerable morphological heterogeneity and a oredominance of APL variants with unfavourable oresenting features.

  13. Targeting MTHFD2 in acute myeloid leukemia.

    Science.gov (United States)

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M; Frumm, Stacey M; Ross, Linda; Fenouille, Nina; Bassil, Christopher F; Lewis, Caroline A; Ramos, Azucena; Gould, Joshua; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene; Clish, Clary B; Kung, Andrew L; Hemann, Michael T; Vander Heiden, Matthew G; Banerji, Versha; Stegmaier, Kimberly

    2016-06-27

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. © 2016 Pikman et al.

  14. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia.

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C; Moura, Ivan C; Hermine, Olivier

    2010-04-12

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.

  15. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C.

    2010-01-01

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML. PMID:20368581

  16. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

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

  17. Expression of CD133 in acute leukemia.

    Science.gov (United States)

    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.

  18. Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-16

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

  19. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Transfer of multidrug resistance among acute myeloid leukemia cells via extracellular vesicles and their microRNA cargo.

    Science.gov (United States)

    Bouvy, Céline; Wannez, Adeline; Laloy, Julie; Chatelain, Christian; Dogné, Jean-Michel

    2017-11-01

    The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested. The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multi-resistant strain, HL60/AR that overexpresses the multidrug resistance protein 1 (MRP-1). A chemo-resistance transfer between the two strains was established by treating HL60 cells with EVs generated by HL60/AR. This study reveals that EVs from HL60/AR can interact with HL60 cells and transfer at least partially, their chemo-resistance. EVs-treated cells begin to express MRP-1 probably due to a direct transfer of MRP-1 and nucleic acids transported by EVs. In this context, two microRNAs were highlighted for their high differential expression in EVs related to sensitive or chemo-resistant cells: miR-19b and miR-20a. Because circulating microRNAs are found in all biological fluids, these results bring out their potential clinical use as chemo-resistance biomarkers in acute myeloid leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  2. Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. APL Study Group. Acute promyelocytic leukemia.

    Science.gov (United States)

    Thomas, X; Dombret, H; Cordonnier, C; Pigneux, A; Gardin, C; Guerci, A; Vekhoff, A; Sadoun, A; Stamatoullas, A; Fegueux, N; Maloisel, F; Cahn, J Y; Reman, O; Gratecos, N; Berthou, C; Huguet, F; Kotoucek, P; Travade, P; Buzyn, A; de Revel, T; Vilque, J P; Naccache, P; Chomienne, C; Degos, L; Fenaux, P

    2000-06-01

    The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging.

  3. The MLL recombinome of acute leukemias in 2017

    DEFF Research Database (Denmark)

    Meyer, C; Burmeister, T; Gröger, D

    2018-01-01

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

  4. Acute myeloid leukemia: advances in diagnosis and classification.

    Science.gov (United States)

    Hasserjian, R P

    2013-06-01

    Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans. © 2013 Blackwell Publishing Ltd.

  5. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    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.

  6. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  7. Epigenetic analysis of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Dunwell, Thomas L; Hesson, Luke B; Pavlova, Tatiana; Zabarovska, Veronika; Kashuba, Vladimir; Catchpoole, Daniel; Chiaramonte, Raffaella; Brini, Anna T; Griffiths, Mike; Maher, Eamonn R; Zabarovsky, Eugene; Latif, Farida

    2009-04-01

    We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B", alpha) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, beta) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2'-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.

  8. Induction of mitochondrial dependent apoptosis and cell cycle arrest in human promyelocytic leukemia HL-60 cells by an extract from Dorstenia psilurus: a spice from Cameroon

    Science.gov (United States)

    2013-01-01

    Background The use of edible plants is an integral part of dietary behavior in the West region of Cameroon. Dorstenia psilurus (Moraceae) is widely used as spice and as medicinal plant for the treatment of several diseases in Cameroon. The aim of this study is to investigate the cytotoxic and apoptotic potential of methanol extract of D. psilurus in human promyelocytic leukemia (HL-60) cells and prostate cancer (PC-3) cells. Methods Cytotoxicity of D. psilurus extract was tested in HL-60 and PC-3 cells using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and flow cytometric methods Results The methanol extract of D. psilurus have significant in vitro cytotoxic activity in HL-60 cells and PC-3 cells with IC50 value of 12 ±1.54 μg/ml and 18 ± 0.45 μg/ml respectively after 48 h. The mechanism of antiproliferative activity showed that after 24 h, D. psilurus extract induces apoptosis on HL-60 cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, modification in the DNA distribution and enhance of G2/M phase cell cycle. Conclusion The extract induces apoptosis of HL-60 cells associated with ROS production, loss of mitochondrial membrane potential and apoptotic DNA fragmentation. PMID:24016040

  9. The cellular prion protein: a new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells.

    Science.gov (United States)

    Rybner, C; Finel-Szermanski, S; Felin, M; Sahraoui, T; Rousseau, C; Fournier, J G; Sève, A P; Botti, J

    2002-01-01

    Prion diseases are characterized by the presence of an abnormal isoform of the cellular prion protein (PrPc) whose physiological role still remains elusive. To better understand the function of PrPc, it is important to identify the different subcellular localization(s) of the protein and the different partners with which it might be associated. In this context, the PrPc-lectins interactions are investigated because PrPc is a sialoglycoprotein which can react with lectins which are carbohydrate-binding proteins. We have previously characterized a nuclear lectin CBP70 able to recognize N-acetyl-beta-D-glucosamine residues in HL60 cells. Using confocal immunofluorescence, flow-cytofluorometry, and Western-blotting, we have found that PrPc is expressed in the nucleus of the NB4 human promyelocytic leukemia cell line. It was also found that the lectin CBP70 is localized in NB4 cell nuclei. Moreover, several approaches revealed that PrPc and CBP70 are colocalized in the nucleus. Immunoprecipitation experiments showed that these proteins are coprecipitated and interact via a sugar-dependent binding moiety. In conclusion, PrPc and CBP70 are colocalized in the nuclear compartment of NB4 cells and this interaction may be important to better understand the biological function and possibly the conversion process of PrPc into its pathological form (PrPsc). Copyright 2001 Wiley-Liss, Inc.

  10. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA

    International Nuclear Information System (INIS)

    Wickstrom, E.L.; Bacon, T.A.; Gonzalez, A.; Freeman, D.L.; Lyman, G.H.; Wickstrom, E.

    1988-01-01

    The human promyelocytic leukemia cell line HL-60 overexpresses the c-myc protooncogene. A calculated secondary structure for c-myc mRNA placed the initiation codon in a bulge of a weakly based-paired region. Treatment of HL-60 cells with 5' d(AACGTTGAGGGGCAT) 3', complementary to the initiation codon and the next four codons of c-myc mRNA, inhibited c-myc protein expression in a dose-dependent manner. However, treatment of HL-60 cells with 5' d(TTGGGATAACACTTA) 3', complementary to nucleotides 17-31 of vesicular stomatits virus matrix protein mRNA, displayed no such effects. These results agree with analogous studies of normal human T lymphocytes, except that only one-third as much oligomer was needed for a comparable effect. Proliferation of HL-60 cells in culture was inhibited in a sequence-specific, dose-dependent manner by the c-myc-complementary oligomer, but neither the oligomer complementary to vesicular stomatitis virus matrix protein mRNA nor 5' d(CATTTCTTGCTCTCC) 3', complementary to nucleotides 5399-5413 of human immunodeficiency virus tat gene mRNA, inhibited proliferation. It thus appears that antisense oligodeoxynucleotides added to myc-transformed cells via culture medium are capable of eliciting sequence-specific, dose-dependent inhibition of c-myc protein expression and cell proliferation

  11. [Leukemia research in Germany: the Competence Network Acute and Chronic Leukemias].

    Science.gov (United States)

    Kossak-Roth, Ute; Saußele, Susanne; Aul, Carlo; Büchner, Thomas; Döhner, Hartmut; Dugas, Martin; Ehninger, Gerhard; Ganser, Arnold; Giagounidis, Aristoteles; Gökbuget, Nicola; Griesshammer, Martin; Hasford, Jörg; Heuser, Michael; Hiddemann, Wolfgang; Hochhaus, Andreas; Hoelzer, Dieter; Niederwieser, Dietger; Reiter, Andreas; Röllig, Christoph; Hehlmann, Rüdiger

    2016-04-01

    The Competence Network "Acute and Chronic Leukemias" was founded in 1997 by the consolidation of the leading leukemia study groups in Germany. Key results are the development of new trials and cooperative studies, the setup of patient registries and biobanking facilities, as well as the improvement of study infrastructure. In 2003, the concept of the competence network contributed to the foundation of the European LeukemiaNet (ELN). Synergy with the ELN resulted in cooperation on a European and international level, standardization of diagnostics and treatment, and recommendations for each leukemia and interdisciplinary specialty. The ultimate goal of the network is the cure of leukemia through cooperative research.

  12. Leukemia

    International Nuclear Information System (INIS)

    Mabuchi, Kiyohiko; Kusumi, Shizuyo

    1992-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

  14. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  15. Nanomedicine approaches in acute lymphoblastic leukemia.

    Science.gov (United States)

    Tatar, Andra-Sorina; Nagy-Simon, Timea; Tomuleasa, Ciprian; Boca, Sanda; Astilean, Simion

    2016-09-28

    Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting. Nanomedicine approaches, especially by the use of nanoparticle-based compounds for the delivery of drugs, cancer diagnosis or therapeutics may represent new and modern ways in the near future anti-cancer therapies. This review offers an overview on the recent role of nanomedicine in the detection and treatment of acute lymphoblastic leukemia as resulting from a thorough literature survey. A short introduction on the basics of ALL is presented followed by the description of the conventional methods used in the ALL detection and treatment. We follow our discussion by introducing some of the general nano-strategies used for cancer detection and treatment. The detailed role of organic and inorganic nanoparticles in ALL applications is further presented, with a special focus on gold nanoparticle-based nanocarriers of antileukemic drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Solubility shift and SUMOylaltion of promyelocytic leukemia (PML) protein in response to arsenic(III) and fate of the SUMOylated PML

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Seishiro, E-mail: seishiro@nies.go.jp [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Tadano, Mihoko [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Kobayashi, Yayoi [Center for Environmental Health Sciences, National Institute for Environmental Studies (Japan); Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Udagawa, Osamu [Center for Environmental Risk Research, National Institute for Environmental Studies (Japan); Kato, Ayaka [Graduate School of Pharmaceutical Sciences, Chiba University (Japan)

    2015-09-15

    Promyelocytic leukemia (PML), which is a tumor suppressor protein that nevertheless plays an important role in the maintenance of leukemia initiating cells, is known to be biochemically modified by As{sup 3+}. We recently developed a simple method to evaluate the modification of PML by As{sup 3+} resulting in a change in solubility and the covalent binding of small ubiquitin-like modifier (SUMO). Here we semi-quantitatively investigated the SUMOylation of PML using HEK293 cells which were stably transfected with PML-VI (HEK-PML). Western blot analyses indicated that PML became insoluble in cold RadioImmunoPrecipitation Assay (RIPA) lysis buffer and was SUMOylated by both SUMO2/3 and SUMO1 by As{sup 3+}. Surprisingly SUMO1 monomers were completely utilized for the SUMOylation of PML. Antimony (Sb{sup 3+}) but not bismuth (Bi{sup 3+}), Cu{sup 2+}, or Cd{sup 2+} biochemically modified PML similarly. SUMOylated PML decreased after removal of As{sup 3+} from the culture medium. However, unSUMOylated PML was still recovered in the RIPA-insoluble fraction, suggesting that SUMOylation is not requisite for changing the RIPA-soluble PML into the RIPA-insoluble form. Immunofluorescence staining of As{sup 3+}-exposed cells indicated that SUMO2/3 was co-localized with PML in the nuclear bodies. However, some PML protein was present in peri-nuclear regions without SUMO2/3. Functional Really Interesting New Gene (RING)-deleted mutant PML neither formed PML nuclear bodies nor was biochemically modified by As{sup 3+}. Conjugation with intracellular glutathione may explain the accessibility of As{sup 3+} and Sb{sup 3+} to PML in the nuclear region evading chelation and entrapping by cytoplasmic proteins such as metallothioneins. - Highlights: • As{sup 3+} is a carcinogen and also a therapeutic agent for leukemia. • PML becomes insoluble in RIPA and SUMOylated by As{sup 3+}. • Sb{sup 3+} modifies PML similar to As{sup 3+}. • Functional RING motif is necessary for As{sup 3

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

    Science.gov (United States)

    2017-06-27

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

  18. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-12-04

    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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

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

    Science.gov (United States)

    2014-08-26

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

  20. Cranial computerized tomography in children suffering from acute leukemia

    International Nuclear Information System (INIS)

    Metz, O.

    1981-01-01

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

  1. Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

    Science.gov (United States)

    Wennström, Lovisa; Edslev, Pernille Wendtland; Abrahamsson, Jonas; Nørgaard, Jan Maxwell; Fløisand, Yngvar; Forestier, Erik; Gustafsson, Göran; Heldrup, Jesper; Hovi, Liisa; Jahnukainen, Kirsi; Jonsson, Olafur Gisli; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Holmberg, Erik; Juliusson, Gunnar; Stockelberg, Dick; Hasle, Henrik

    2016-01-01

    Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols. © 2015 Wiley Periodicals, Inc.

  2. [Infections in the child with acute leukemia].

    Science.gov (United States)

    Carrillo, J M; Jiménez, E; Jiménez, R

    1981-01-01

    One hundred and twenty-five febrile episodes in 82 children with acute leukemia were studied; 46% of the patients were from urban and 54% from rural areas. The origin of the fever was identified in 91% of the episodes, prevailing pneumonia, septicemia, chickenpox and herpes zoster. The etiological agent was identified in 46% of the cases. A viral predominance was evident, and among them varicela-zoster, following in importance gram-negative bacteria. Histoplasma capsulatum and Pneumocystis carinii were isolated in two occassions each. Sepsis was found more frequently in children with active leukemia than in those in remission (p less than 0.001). Forty-four febrile episodes occurred in patients with less than 1,000 neutrophils/ul. The daily-risk rate of infection was higher in children fom rural than in those from urban areas (p less than 0.001). After clinical and laboratory studies, methicillin and gentamicin were used, in addition to carbenicillin or trimethoprim-sulfamethoxazole is selected cases. This treatment was effective in 86% of the cases. Twelve (15%) children died, 6 of whom were in remission at that moment.

  3. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

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    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

  4. Recurrent Cytogenetic Abnormalities in Acute Myeloid Leukemia.

    Science.gov (United States)

    Yang, John J; Park, Tae Sung; Wan, Thomas S K

    2017-01-01

    The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification. Brief morphologic, cytogenetic, and clinical characteristics are summarized, so as to provide a concise reference to cancer cytogenetic laboratories. Morphology based on FAB classification is used together with the current WHO classification due to frequent mentioning in a vast number of reference literatures. Characteristic chromosomal aberrations of other myeloid neoplasms such as myelodysplastic syndrome and myeloproliferative neoplasm will be discussed in separate chapters-except for certain abnormalities such as t(9;22) in de novo AML. Gene mutations detected in normal karyotype AML by cutting edge next generation sequencing technology are also briefly mentioned.

  5. Emerging therapies for acute myeloid leukemia

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    Caner Saygin

    2017-04-01

    Full Text Available Abstract Acute myeloid leukemia (AML is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH inhibitors, vadastuximab or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin, epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC inhibitors, bromodomain and extraterminal (BET inhibitors, FMS-like tyrosine kinase receptor 3 (FLT3 inhibitors, and antibody-drug conjugates (vadastuximab, as well as cell cycle inhibitors (volasertib, B-cell lymphoma 2 (BCL-2 inhibitors, and aminopeptidase inhibitors. These agents are actively undergoing clinical investigation alone or in combination with available chemotherapy.

  6. Current Management of Childhood Acute Myeloid Leukemia.

    Science.gov (United States)

    Rubnitz, Jeffrey E

    2017-02-01

    The outcome for children with acute myeloid leukemia (AML) has improved significantly over the past 30 years, with complete remission and overall survival rates exceeding 90 and 60%, respectively, in recent clinical trials. However, these improvements have not been achieved by the introduction of new agents. Instead, intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy have all contributed to this success. Nevertheless, novel therapies are needed, as the cure rates for many subtypes of childhood AML remain unacceptably low. Here, we briefly review advances in our understanding of the biology and genetics of AML, the results of recent clinical trials, and current recommendations for the treatment of children with AML.

  7. Computed tomographic findings of intracranial acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dong Woo; Ryu, Weon Don; Kim, Jong Sung; Koh, Byung Hee; Jeon, Seok Chol; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1990-07-15

    Computed tomographic (CT) abnormalities in the brain were retrospectively analyzed in 16 of 103 patients with acute leukemia confirmed by CSF cytology or combined surgery at Hanyang University Hospital, from August 1980 to August 1989. The results were as follows : 1. With FAB classification, the most frequent pathologic type was L1 : 8 cases (50%) 2. The range of age distribution showed typical pattern that ALL occurred below the 15 years old, and AML, over 15 years old. 3. Abnormal CT findings were ; Meningitis(2 cases), Mass(3), Thrombosis(1), Infarction(2), Edema(1), Hemorrhage(7), Hydrocephalus(2), Atrophy(2). 4. Most of infracranial hemorrhage were seen in M{sub 2} and M{sub 3} type.

  8. Osteogenesis imperfecta and acute lymphoid leukemia: case report

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    Gabriel David Tarud

    2017-08-01

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

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

    Science.gov (United States)

    Yan, Ying; Wieman, Eric A; Guan, Xiuqin; Jakubowski, Ann A; Steinherz, Peter G; O'Reilly, Richard J

    2009-12-29

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...

  12. Cytotoxicity, Antiproliferative Effects, and Apoptosis Induction of Methanolic Extract of Cynometra cauliflora Linn. Whole Fruit on Human Promyelocytic Leukemia HL-60 Cells

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    T-Johari S. A. Tajudin

    2012-01-01

    Full Text Available Methanolic extract of Cynometra cauliflora whole fruit was assayed for cytotoxicity against the human promyelocytic leukemia HL-60 and the normal mouse fibroblast NIH/3T3 cell lines by using the MTT assay. The CD50 of the extract for 72 hours was 0.9 μg/mL whereas the value for the cytotoxic drug vincristine was 0.2 μg/mL. The viability of the NIH/3T3 cells was at 80.0% when treated at 15.0 μg/mL. The extract inhibited HL-60 cell proliferation with dose dependence. AO/PI staining of HL-60 cells treated with the extract revealed that majority of cells were in the apoptotic cell death mode. Flow cytometry analysis of HL-60 cells treated at CD50 of the extract showed that the early apoptotic cells were 31.0, 26.3 and 19.9% at 24, 48, and 72 hours treatment, respectively. The percentage of late apoptotic cells was increased from 62.0 at 24 hours to 64.1 and 70.2 at 48 and 72 hours, respectively. Meanwhile, percent of necrotic cells were 4.9, 6.6, and 8.5 at 24, 48, and 72 hours, respectively. This study has shown that the methanolic extract of C. cauliflora whole fruit was cytotoxic towards HL-60 cells and induced the cells into apoptotic cell death mode, but less cytotoxic towards NIH/3T3 cells.

  13. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  14. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    F.P.G. Silva (Fernando); I. Almeida (Inês); B. Morolli (Bruno); G. Brouwer-Mandema (Geeske); H. Wessels (Hans); R. Vossen (Rolf); H. Vrieling (Harry); E.W.A. Marijt (Erik); P.J.M. Valk (Peter); J.C. Kluin-Nelemans (Hanneke); W.R. Sperr (Wolfgang); W.D. Ludwig; M. Giphart-Gassler (Micheline)

    2009-01-01

    textabstractBackground: Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when

  15. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    Silva, Fernando P. G.; Almeida, Ines; Morolli, Bruno; Brouwer-Mandema, Geeske; Wessels, Hans; Vossen, Rolf; Vrieling, Harry; Marijt, Erik W. A.; Valk, Peter J. M.; Kluin-Nelemans, Hanneke C.; Sperr, Wolfgang R.; Ludwig, Wolf-Dieter; Giphart-Gassler, Micheline

    2009-01-01

    Background Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when other

  16. Chronic Subdural Hematoma Associated with Acute Biphenotypic Leukemia: Case Report

    OpenAIRE

    Besime Utku; Uygar Utku

    2015-01-01

    Spontaneous chronic subdural hematoma associated with neoplasm is a rare disorder. A rare case of chronic subdural hematoma associated with acute biphenotypic leukemia presented here. A 78-year-old woman who diagnosed as acute biphenotypic leukemia by hematology was complicated with a large chronic subdural hematoma. She presented to our emergency medicine service of hospital with left-sided weakness. Her non-contrast brain computerized tomography scan showed a non-traumatic right-sided, larg...

  17. Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Devesh Kumawat

    2018-01-01

    Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

  18. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according to cytog......Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  19. [Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

    Science.gov (United States)

    Matsuda, Isao; Nakamaki, Tsuyoshi; Amaya, Hiroshi; Kiyosaki, Masanobu; Kawakami, Keiichiro; Yamada, Kazunari; Yokoyama, Akihiro; Hino, Ken-ichiro; Tomoyasu, Shigeru

    2003-09-01

    A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

  20. Identification of an MLC suppressor cell population in acute leukemia

    International Nuclear Information System (INIS)

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

    1978-01-01

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

  1. Infections in acute leukemia in Indian Children

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    B Roy

    2014-01-01

    Full Text Available Aims: In the present study acute leukemic children were studied to determine the incidence and principal site of infection, correlation with absolute neutrophil count, causative organisms and to standardize the initial empirical anti microbial therapy. Materials and methods: A total 40 children in the age group 6 month to 12 year with acute leukemia relapse were included in this study. A total 82 infectious episodes including 61 febrile episodes were investigated for infectious etiology. Results: We found that the frequency of infections increased significantly with the degree of immunocompromisation specially neutropenia (ANC < 500/cmm. The skin and soft tissue was the commonest site of infection (26.83%, followed by respiratory tract (21.95%. Staphylococcus nonhemolytic coagulase-negative (34%, followed by Klebsiella (17% were the most common organisms isolated from blood. Staphylococcus non-hemolytic coagulase-negative was also the commonest isolate (26% from other sites of infection. Most strains were sensitive to Cloxacillin, cephalosporin and aminoglycosides. Conclusion: For the treatment of febrile episodes, empirical use of beta-lactamase resistant penicillin e.g. Cloxacillin or cephalosporin combined with an aminoglycosides with a broad spectrum antifungal like fluconazole in selective cases at the first sign of infection is recommended. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 40-47 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9672

  2. Pneumonia during Remission Induction Chemotherapy in Patients with Acute Leukemia

    Science.gov (United States)

    Garcia, Javier Barreda; Lei, Xiudong; Wierda, William; Cortes, Jorge E.; Dickey, Burton F.; Evans, Scott E.

    2013-01-01

    Background: Pneumonia is a major cause of death during induction chemotherapy for acute leukemia. The purpose of this study was to quantify the incidence, risk factors, and outcomes of pneumonia in patients with acute leukemia. Methods: We conducted a retrospective cohort study of 801 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or acute lymphocytic leukemia (ALL) who underwent induction chemotherapy. Measurements and Main Results: Pneumonia was present at induction start in 85 patients (11%). Of the 716 remaining patients, 148 (21%) developed pneumonia. The incidence rate of pneumonia was higher in MDS and AML than in ALL (0.013 vs. 0.008 vs. 0.003 pneumonias per day, respectively; P risk factors. The case fatality rate of pneumonia was 17% (40 of 233). Competing risk analysis demonstrated that in the absence of pneumonia, death was rare: 28-day mortality was 6.2% for all patients but only 1.26% in those without pneumonia. Compared with patients without pneumonia, patients with pneumonia had more intensive care unit days, longer hospital stays, and 49% higher costs (P Pneumonia after induction chemotherapy for acute leukemia continues to be common, and it is the most important determinant of early mortality after induction chemotherapy. Given the high incidence, morbidity, mortality, and cost of pneumonia, interventions aimed at prevention are warranted in patients with acute leukemia. PMID:23987587

  3. [Our experiences in the treatment of acute leukemias].

    Science.gov (United States)

    Jelić, S; Dragović, M; Vidaković, B; Plecas, V

    1976-01-01

    This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.

  4. ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CIRCULATING BLASTS PRESENTING AS SEVERE HYPERCALCEMIA

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    Z. Oloomi

    2007-05-01

    Full Text Available Hypercalcemia complicating malignancy is a rare complication in pediatric age group. In this article, we present a case with acute lymphoblastic leukemia presenting as severe hypercalcemia. A 10 years old girl presented with an acute onset of fever, nausea, vomiting, loss of weight, costovertebral pain and frequency. She was admitted with a presumptive diagnosis of acute pyelonephritis. Her examination showed mild hepatosplenomegaly. In laboratory studies she had sever hypercalcemia. Despite the absence of circulating blast, bone marrow aspiration was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide but the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in differential diagnosis even when there are no circulating blasts.

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

    Science.gov (United States)

    2017-08-18

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

  6. Evaluation of Serum Leptin Level in Children With Acute Leukemia

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    Iraj Shahramian

    2016-01-01

    Full Text Available Background Leptin is a multifunctional hormone plays an important role in regulating lipid, energy, homeostasis, angiogenesis, inflammation, hematopoiesis and cell cycle. This polypeptide is effective in growth and differentiation of leukemic cells through an Ob-R receptor expressed by them. Objectives The purpose of this study was to evaluate serum leptin levels in patients with acute leukemia and compare it in lymphoid and myeloid groups. Patients and Methods This analytical case-control study, conducted on 60 children in age ranged from 6 months to 16 years in two case and control groups in Ali ibn Abi Talib hospital, Zahedan. They matched based on age and gender and examined after their parent’s satisfaction according to the parental consent forms. None of patients had heart disease, digestive, glandular and metabolic problems, iron deficiency anemia and chronic kidney disease. After collecting the samples, leptin levels of both groups were measured with ELISA kit. Then, the gathered data were analyzed in SPSS-20 software, using independent t-test in considering of 95% confidence interval. Results Leptin serum levels in patients with acute leukemia and controls showed significant difference (P < 0.05. Leptin serum levels in patients with acute lymphoblastic leukemia and acute myeloblastic leukemia showed significant difference (P < 0.05. Leptin serum level in relation to age and gender groups was not statistically significant. Conclusions The findings of this study showed that in patients with acute leukemia, leptin serum levels increase independently of age and gender. In addition, leptin serum levels in acute lymphoid leukemia were higher than acute myeloid leukemia in this study.

  7. [Acute leukemias epidemiology in children. Part 1].

    Science.gov (United States)

    Mejía Aranguré, Juan Manuel; Ortega Alvarez, Manuel Carlos; Fajardo Gutiérrez, Arturo

    2005-01-01

    This paper is a revision from recent studies related to acute leukemia (AL) epidemiology in children. Cancer is the second cause of death in the pediatric population in Mexico between 1 to 15 years old. The AL are the types of cancer with more frequency in children below 15 years old and the cost of taking care of a child with cancer represents to the health institutions around 620 thousand dollars per year per case. In different places of the world the frequency of the AL has been increased and in Mexico City this is similar. Data from Instituto Mexicano del Seguro Social, in Mexico City, reports one of the highest worldwide. The environmental risk factors most consistent are the exposure in utero to X-ray, occupational exposure and pesticides. Other risk factors studied, as the exposure to electromagnetic fields, smoking and alcohol consumption in the parents, diet, and others, have had controversial results. These controversies can be explained by methodological mistakes in the studies and also because these studies did not assess the interaction between the susceptibility to AL and the environmental factors, a situation that could lead to the better understanding of the causal mechanisms of the disease. However it is recommended to have an attitude of prudent caution to accept that these factors are a cause of AL, and to have an energetic position in order to decrease the exposure to them and produce more adequate preventive strategies.

  8. The Epigenetic Landscape of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    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.

  9. Novel therapeutic options in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Especially for patients with intermediate or high-risk AML, which often show relapse. Allogeneic hematopoietic stem cell transplantation (HSCT remains the best chance for cure. Here we review the state of the art therapy of AML, with special focus on new developments in immunotherapies and cellular therapies including HSCT and particularly discuss the impact of new conditioning and haplo-identical donor regimens for HSCT, post-transplant strategies for preventing and treating relapse, and emerging novel therapeutic options.

  10. Unfavorable-risk acute myeloid leukemia dissected.

    Science.gov (United States)

    Strickland, Stephen A; Mohan, Sanjay R; Savona, Michael R

    2016-03-01

    Acute myeloid leukemia (AML) is an immensely heterogeneous disease based on the presence of varying combinations of morphologic, immunophenotypic, genetic, and molecular characteristics identified among those diagnosed with this disease. Although current therapeutic strategies provide a reasonable likelihood of achieving a complete remission for the majority of patients, relapse rates and subsequent disease-related mortality remain unacceptably high. Improved methods of risk stratification are needed to better identify patients at considerable risk of relapse in hopes of allowing for early therapeutic intervention and/or intensification that may lead to a higher likelihood of cure. The current status of risk stratification of AML and emerging technologies with potential to improve prognostic classification and outcomes are summarized in this review. Refinement of our understanding of the impact of current pretreatment AML cytogenetic, immunophenotypic, and molecular aberrations to predict outcomes and guide therapeutic decision-making is ongoing. Emerging data suggest that incorporation of the degree of posttreatment response and/or the detection of minimal residual disease can improve the accuracy of risk stratification for individual patients. Although pretreatment disease characteristics remain the hallmark of prognostication for AML patients, posttreatment parameters such as minimal residual disease assessment and degree of response to therapy possess the ability to further refine our identification of patients with unfavorable disease and thereby influence decisions regarding therapeutic planning.

  11. Acute Lymphoblastic Leukemia, Version 2.2015.

    Science.gov (United States)

    Alvarnas, Joseph C; Brown, Patrick A; Aoun, Patricia; Ballen, Karen Kuhn; Barta, Stefan K; Borate, Uma; Boyer, Michael W; Burke, Patrick W; Cassaday, Ryan; Castro, Januario E; Coccia, Peter F; Coutre, Steven E; Damon, Lloyd E; DeAngelo, Daniel J; Douer, Dan; Frankfurt, Olga; Greer, John P; Johnson, Robert A; Kantarjian, Hagop M; Klisovic, Rebecca B; Kupfer, Gary; Litzow, Mark; Liu, Arthur; Rao, Arati V; Shah, Bijal; Uy, Geoffrey L; Wang, Eunice S; Zelenetz, Andrew D; Gregory, Kristina; Smith, Courtney

    2015-10-01

    Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. Copyright © 2015 by the National Comprehensive Cancer Network.

  12. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  13. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Alternative Donor Transplantation for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nelli Bejanyan

    2015-06-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT is a potentially curative therapy for adult patients with acute myeloid leukemia (AML, but its use for consolidation therapy after first remission with induction chemotherapy used to be limited to younger patients and those with suitable donors. The median age of AML diagnosis is in the late 60s. With the introduction of reduced-intensity conditioning (RIC, many older adults are now eligible to receive allo-HCT, including those who are medically less fit to receive myeloablative conditioning. Furthermore, AML patients commonly have no human leukocyte antigen (HLA-identical or medically suitable sibling donor available to proceed with allo-HCT. Technical advances in donor matching, suppression of alloreactivity, and supportive care have made it possible to use alternative donors, such as unrelated umbilical cord blood (UCB and partially HLA-matched related (haploidentical donors. Outcomes after alternative donor allo-HCT are now approaching the outcomes observed for conventional allo-HCT with matched related and unrelated donors. Thus, with both UCB and haploidentical donors available, lack of donor should rarely be a limiting factor in offering an allo-HCT to adults with AML.

  15. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Amit Pande

    2016-01-01

    Full Text Available Background: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. Materials and Methods: We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML, 13 were precursor B-acute lymphoblastic leukemia (B-ALL, 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid as per the WHO classification. Results: We found that the expression of CD71 was most prevalent in AMLs (84%, followed by T-ALL (50% and least in B-ALL (30%. Conclusion: This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

  16. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia.

    Science.gov (United States)

    Pande, Amit; Dorwal, Pranav; Jain, Dharmendra; Tyagi, Neetu; Mehra, Simmi; Sachdev, Ritesh; Raina, Vimarsh

    2016-01-01

    CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid) as per the WHO classification. We found that the expression of CD71 was most prevalent in AMLs (84%), followed by T-ALL (50%) and least in B-ALL (30%). This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

  17. Arsenic Trioxide and Tretinoin (AsO/ATRA) for Acute Promyelocytic Leukemia (APL)

    Science.gov (United States)

    Damery, Erin; Solimando, Dominic A.; Waddell, J. Aubrey

    2016-01-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110–545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID:27698500

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shi Hao Tan

    2017-09-01

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

  20. Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells.

    Science.gov (United States)

    Petrov, Ivan; Suntsova, Maria; Mutorova, Olga; Sorokin, Maxim; Garazha, Andrew; Ilnitskaya, Elena; Spirin, Pavel; Larin, Sergey; Kovalchuk, Olga; Prassolov, Vladimir; Zhavoronkov, Alex; Roumiantsev, Alexander; Buzdin, Anton

    2016-11-19

    Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

  1. Kaempferol induces DNA damage and inhibits DNA repair associated protein expressions in human promyelocytic leukemia HL-60 cells.

    Science.gov (United States)

    Wu, Lung-Yuan; Lu, Hsu-Feng; Chou, Yu-Cheng; Shih, Yung-Luen; Bau, Da-Tian; Chen, Jaw-Chyun; Hsu, Shu-Chun; Chung, Jing-Gung

    2015-01-01

    Numerous evidences have shown that plant flavonoids (naturally occurring substances) have been reported to have chemopreventive activities and protect against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely distributed in fruits and vegetables, and may have cancer chemopreventive properties. However, the precise underlying mechanism regarding induced DNA damage and suppressed DNA repair system are poorly understood. In this study, we investigated whether kaempferol induced DNA damage and affected DNA repair associated protein expression in human leukemia HL-60 cells in vitro. Percentages of viable cells were measured via a flow cytometry assay. DNA damage was examined by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA gel electrophoresis. The changes of protein levels associated with DNA repair were examined by Western blotting. Results showed that kaempferol dose-dependently decreased the viable cells. Comet assay indicated that kaempferol induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also showed increased doses of kaempferol which led to increased DNA condensation, these effects are all of dose-dependent manners. Western blotting indicated that kaempferol-decreased protein expression associated with DNA repair system, such as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia-telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O(6)-methylguanine-DNA methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the protein expression of p-p53 and p-H2AX. Protein translocation was examined by confocal laser microscopy, and we found that kaempferol increased the levels of p-H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA repair associated protein expression in HL-60

  2. A case report of acute myeloid leukemia and neurofibromatosis 1

    Directory of Open Access Journals (Sweden)

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a 65-year old patient affected by neurofibromatosis 1, documented by the presence of germ-line mutation on the NF1 gene, who developed various hyperproliferative malignant and benign diseases. He was brought to our attention for the diagnosis of acute myeloid leukemia revealed by major fatigue and dyspnea. The disease characteristics at diagnosis were hyperleukocytosis and complex karyotype with the inversion of the chromosome 16, classifying as a high-risk leukemia. The association between leukemia and neurofibromatosis 1 is controversial and needs to be further investigated. Nevertheless, such patients present a wide number of comorbidities that make therapeutic strategies most difficult.

  3. Temozolomide and cisplatin in relapsed/refractory acute leukemia

    Directory of Open Access Journals (Sweden)

    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.

  4. Leukemia

    International Nuclear Information System (INIS)

    Kamada, Nanao

    1992-01-01

    This chapter deals with clinical features associated with chromosomal aberration in A-bomb survivors with leukemia. Clinical features are presented by dividing them into three categories: (1) those from preleukemic stage up to the development of overt leukemia, (2) those specific to A-bomb survivors, and (3) changes in chromosomes. Many of the A-bomb survivors had normocytic anemia and leukopenia for a long time preceding the development of overt leukemia. A woman exposed to 483 rad (estimated by the T65D) 800 m from the hypocenter who finally developed erythroleukemia is presented; and in 6 other A-bomb survivors, abnormal hematological findings up to the development of overt acute leukemia are mentioned. Hematological findings in chronic myeloid leukemia (CML) are discussed by presenting two cases: one was exposed at 800 m from the hypocenter and developed CML 35 years later and the other was exposed at 1800 m and developed it 22 years later. In A-bomb survivors, acute leukemia tended to be associated with smaller number of leukemic cells in both peripheral blood and bone marrow, and non-leukemic leukemia was observed. Chromosomal analysis has been made in 75 A-bomb survivors with acute leukemia and 55 CML A-bomb survivors. In acute leukemic patients exposed to one Gy or more, bone marrow stem cells with chromosomal aberrations occurring at the time of exposure were considered to be proliferated by various factors. A-bomb survivors with CML are found to be characterized by having Philadelphia chromosome, t(9;22)(q34;q11). (N.K.)

  5. CT findings of brain atrophy after chemotherapy in acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jun; Park, Seog Hee; Kim, Choon Yul; Bahk, Yong Whee [Catholic University Medicine College, Seoul (Korea, Republic of)

    1988-10-15

    A study was performed to evaluate the atrophic changes of the central nerve system after chemotherapy in the patients with acute leukemia. The computed tomographic findings and medical records of 20 proven acute leukemia patients under 35 years-old who developed various CNS symptoms and signs during and/or after 2 courses of chemotherapy were reviewed. The results were as follows: 1. Age distribution was from 14 to 5 years (mean was 26 years). Male was 15. 2. Presenting clinical symptoms and signs were headache (16/20), nausea and vomiting (11/20) and loss of consciousness (5/20). 3. Brain atrophy was noted in 16 patients including cortical and subcortical atrophy 15 cases and subcortical atrophy 1 case. 4. Two cases of hemorrhage, one each of intracranial hematoma and chronic subdural hematoma were found in addition to brain atrophy. This showed that chemotherapeutic agents cause brain atrophy in a considerable number of the patients with symptomatic acute leukemia.

  6. Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute myeloid leukemia patients

    International Nuclear Information System (INIS)

    Elsayed, Gh.M.; Zaher, A.; Elnoshokaty, E.H.; Nassar, H.R.; Moneer, M.M.

    2014-01-01

    Background: Somatic mutations in isocitrate dehydrogenase 1 (1DH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique. Aim of the work: The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML. Methods: Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDHl gene, codon 132 mutations screening. Results: The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p = 0.03). Patients with 1DH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p = 0.08). Conclusion: IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDF11 mutations in AML.

  7. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  8. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  9. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  10. General Information about Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... lessened. Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received ...

  11. General Information about Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  12. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  13. Treatment Options for Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

  14. Stages of Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... used to determine if the leukemia has spread: Lumbar puncture : A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column . This is done by placing a needle between ...

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

    Science.gov (United States)

    ... 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 ...

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

    DEFF Research Database (Denmark)

    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...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  17. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    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. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    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...

  19. The MLL recombinome of acute leukemias in 2013.

    Science.gov (United States)

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

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Pérez-Saldivar, María Luisa; Fajardo-Gutiérrez, Arturo; Bernáldez-Ríos, Roberto; Martínez-Avalos, Armando; Medina-Sanson, Aurora; Espinosa-Hernández, Laura; Flores-Chapa, José de Diego; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; Alvarez-Rodríguez, Francisco Javier; Bolea-Murga, Victoria; Flores-Lujano, Janet; Rodríguez-Zepeda, María Del Carmen; Rivera-Luna, Roberto; Dorantes-Acosta, Elisa María; Jiménez-Hernández, Elva; Alvarado-Ibarra, Martha; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Duarte-Rodríguez, David Aldebarán; Paredes-Aguilera, Rogelio; Del Campo-Martínez, María de Los Ángeles; Cárdenas-Cardos, Rocío; Alamilla-Galicia, Paola Hillary; Bekker-Méndez, Vilma Carolina; Ortega-Alvarez, Manuel Carlos; Mejia-Arangure, Juan Manuel

    2011-08-17

    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. 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). 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 classified as high risk. There was a positive

  2. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

  3. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    OpenAIRE

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the...

  4. Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia.

    Science.gov (United States)

    Bradstock, Kenneth F; Link, Emma; Di Iulio, Juliana; Szer, Jeff; Marlton, Paula; Wei, Andrew H; Enno, Arno; Schwarer, Anthony; Lewis, Ian D; D'Rozario, James; Coyle, Luke; Cull, Gavin; Campbell, Phillip; Leahy, Michael F; Hahn, Uwe; Cannell, Paul; Tiley, Campbell; Lowenthal, Ray M; Moore, John; Cartwright, Kimberly; Cunningham, Ilona; Taper, John; Grigg, Andrew; Roberts, Andrew W; Benson, Warwick; Hertzberg, Mark; Deveridge, Sandra; Rowlings, Philip; Mills, Anthony K; Gill, Devinder; Bardy, Peter; Campbell, Lynda; Seymour, John F

    2017-05-20

    Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m 2 daily for 5 days, etoposide 75 mg/m 2 daily for 5 days, and idarubicin 9 mg/m 2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3-internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3-internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in

  5. Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Pozdnyakova, Olga; Campigotto, Federico; DeAngelo, Daniel J; Stone, Richard M; Neuberg, Donna; Hasserjian, Robert P

    2015-07-01

    The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.

  6. Serum hepcidin level and disease course of acute leukemia in ...

    African Journals Online (AJOL)

    Acute leukemia (AL) is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is ...

  7. Cutis verticis gyrata secondary to acute monoblastic leukemia.

    Science.gov (United States)

    Passarini, B; Neri, I; Patrizi, A; Masina, M

    1993-04-01

    A 64-year-old man affected by acute monoblastic leukemia developed a cutis verticis gyrata during the terminal phase of hemopathy. The association between these two diseases is rare. The classification of cutis verticis gyrata in primary essential, primary non-essential and secondary forms is reviewed. Performing a skin biopsy is necessary in the diagnostic approach to patients with cutis verticis gyrata.

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

    NARCIS (Netherlands)

    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

  9. Pseudo Chediak-Higashi anomaly in acute myelomonocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rao Seema

    2009-04-01

    Full Text Available Pseudo Chediak-Higashi anomaly in acute leukemia is a rarely described entity. The significance of this intriguing morphological finding largely remains unknown, although some authors have predicted a poorer outcome in such cases because of a higher susceptibility to fulminant infections. Our case also had a fatal outcome.

  10. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...

  11. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2008-01-01

    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, methotrexate...

  12. The MLL recombinome of acute leukemias in 2017

    Science.gov (United States)

    Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. PMID:28701730

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

    Science.gov (United States)

    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.…

  14. VINCRISTINE DISPOSITION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    DEGRAAF, SSN; BLOEMHOF, H; VENDRIG, DEMM; UGES, DRA

    Vincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well-defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new

  15. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    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...

  16. Translational Studies in Elderly Patients with Acute Myeloid Leukemia

    NARCIS (Netherlands)

    B. van der Holt (Bronno)

    2007-01-01

    textabstractThe production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid leukemia (AML) is a clonal disease, which is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a severe

  17. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    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...

  18. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Talibov, Madar; Lehtinen-Jacks, Susanna; Martinsen, Jan Ivar

    2014-01-01

    OBJECTIVE: The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). METHODS: Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden and Iceland from 1961-2005 and 76...

  19. Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

    Directory of Open Access Journals (Sweden)

    Yahui Ding

    2016-09-01

    Full Text Available Abstract Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML are largely attributed to leukemia stem cells (LSCs which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. Methods The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. Results The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C, alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. Conclusions Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.

  20. Survival of patients with mixed phenotype acute leukemias: A large population-based study.

    Science.gov (United States)

    Shi, Runhua; Munker, Reinhold

    2015-06-01

    Little is known about the incidence and treatment outcome of patients with acute biphenotypic leukemias. The World Health Organization (WHO) established the term of acute leukemia of ambiguous phenotype in 2001 (revised in 2008) introducing the term of mixed phenotype acute leukemias. Using the database of the Surveillance, Epidemiology, and End Results registry (SEER), we identified 313 patients with mixed phenotype acute leukemias and compared them with 14,739 patients with acute lymphoblastic leukemia and 34,326 patients with acute myelogenous leukemias diagnosed between 2001 and 2011. As a further control group, 1777 patients were included who were not classified as myeloid, lymphoid or biphenotypic (other acute leukemias). The incidence of mixed phenotype acute leukemias is 0.35 cases/1,000,000 person-years. In a multivariate analysis, the prognosis depends strongly on age (as with other leukemias) and it has the worst outcome of all four types of leukemia. However, the prognosis has improved, comparing 2001-2005 with 2006-2011. We present the first comprehensive, population-based study of acute biphenotypic or mixed phenotype acute leukemias according to the WHO classification. Especially in older patients, the prognosis is unfavorable and new treatments should be investigated. Published by Elsevier Ltd.

  1. IMMUNOLOGICAL CLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIAS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2002-05-01

    Full Text Available Background. ALL is a malignant blood disease and lymphoblasts have origin in B or T lymphatic cell line. In 1997 established new World Health Organisation classification (WHO classification of malignant haematological diseases realizes the importance of cellular immunological markers (immunophenotype and chromosomal abnormalities (cytogenetics. Based on both findings we may distribute the patients in low, intermediate and high risk groups and the outcome of such distribution is risk adopted ALL treatment strategy. On Clinical department of haematology (CDH we have decided to overview immunophenotype characteristics of all ALL patients during the January 1, 1995–December 31, 2001 period.Methods and results. During the January 1, 1995–December 31, 2001 period on CDH we have treated 44 patients: 22 males and 22 females. With flow cytometer Coulter Epics XL MCS we have performed first primary antibody panel for acute leukemias antigens (CD2, CD7, CD10, CD19, CD34, cCD3, cCD13, cCD22, MPO, TdT, followed by secondary panel. The later have included antigen CD20, CD23, membrane and/or cytoplasmatic immunoglobulins or their light chains monoclonal antibodies for B-ALL and antigen CD3, CD4, CD5 and CD8 monoclonal antibodies for T-ALL subsets. Besides immunophenotyping we have evaluated all ALL patients also morphologically according to FAB classification (French-AmericanBritish classification, which is an old classification based solely on morphology.32/44 (73% patients have had immunophenotypic B-ALL, and 12/44 (27% T-ALL. Subgroups distribution of B-ALL immunophenotype were: pro-B 4/44 (9%, »common«-B 18/44 (41%, pre-B 5/44 (11.5% and mature B 5744 (11.5% and for T-ALL immunophenotype were: pro-T 2/44 (4.5%, pre-T 5/44 (11.5%, cortical-T 4/44 (9% and mature-T 1/44 (2%. Our results are quite comparable with the available data from the literature, despite the fact that newest immunological markers such as CD1a, CD79a and CD22 were not available

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

    Directory of Open Access Journals (Sweden)

    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.

  3. BCL11A expression in acute phase chronic myeloid leukemia.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Promyelocytic Sarcoma of the Spine: A Case Report and Review of the Literature

    Science.gov (United States)

    Pacilli, Leonardo; Lo Coco, Francesco; Ramadan, Safaa Mahmoud; Giannì, Laura; Pingi, Alberto; Remotti, Daniele; Majolino, Ignazio

    2010-01-01

    Myeloid sarcoma (MS, previously named granulocytic sarcoma or chloroma) is a rare extramedullary tumour of immature myeloid cells. It can be present before, concurrently with, or after the diagnosis of acute myeloid leukemia. MS is extremely uncommon in acute promyelocytic leukemia (APL). In the case described here, MS was the sole site of APL relapse and the cause of spinal cord compression. The patient presented with neurologic symptoms due to a paravertebral mass of MS after 7 years of complete remission. He was treated with excision of the mass followed by local radiotherapy. Systemic treatment was also given with combined arsenic trioxide and all-trans retinoic acid and the patient was able to achieve a second prolonged clinical and molecular remission. PMID:20339529

  5. Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans.

    Science.gov (United States)

    Robin, Marie; Schlageter, Marie-Hélène; Chomienne, Christine; Padua, Rose-Ann

    2005-10-01

    Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.

  6. [PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia].

    Science.gov (United States)

    Guerra-Castillo, Francisco Xavier; Ramos-Cervantes, María Teresa; Rosel-Pech, Cecilia; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina

    2016-01-01

    In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

  7. Acute erythroid leukemia: autopsy report of a rare disease

    Directory of Open Access Journals (Sweden)

    Cristiane Rúbia Ferreira

    2011-12-01

    Full Text Available Acute erythroid leukemia (AEL is a rare subtype of acute myeloid leukemia(AML, characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO classification of AML defined two AEL subtypes:erythroleukaemia (EL, in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL, in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria.

  8. Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia.

    Science.gov (United States)

    Chisini, Marta; Stefanizzi, Caterina; Ceglie, Teresa; Raponi, Sara; Vozella, Federico; Colafigli, Gioia; Salaroli, Adriano; D'Angiò, Mariella; Mancini, Marco; Diverio, Daniela; Breccia, Massimo; Mancini, Francesca; Minotti, Clara; Trisolini, Silvia; Capria, Saveria; Testi, Anna Maria; Guarini, Anna; Latagliata, Roberto; De Propris, Maria Stefania; Foà, Robin

    2017-12-01

    The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age classification (P = .045), low-risk karyotype (P  8 g/dL (P = .020), and white blood cell < 50 × 10 9 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 9 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  10. Early presentation of osteonecrosis in acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Mogensen, Signe Sloth; Harila-Saari, Arja; Frandsen, Thomas Leth

    2017-01-01

    Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologica......Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms...... and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy....

  11. Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

    Science.gov (United States)

    Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

    2017-01-01

    Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

  12. Diagnostic work-up of acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Sohani, Aliyah R; Bhargava, Parul; Nardi, Valentina

    2017-03-01

    Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment. © 2017 Wiley Periodicals, Inc.

  13. CDX2 gene expression in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

    2014-01-01

    CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  14. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    OpenAIRE

    Góes, Luccas Santos Patto de; Lopes, Roberto Iglesias; Campos, Octavio Henrique Arcos; Oliveira, Luiz Carlos Neves de; Sant’Anna, Alexandre Crippa; Dall’Oglio, Marcos Francisco; Srougi, Miguel

    2014-01-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associat...

  15. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    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%.

  16. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  17. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    International Nuclear Information System (INIS)

    Soares, Maria de Fatima; Braga, Flavio Tulio; Rocha, Antonio Jose da; Lederman, Henrique Manoel

    2005-01-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  18. Leucemia congénita aguda Acute congenital leukemia

    Directory of Open Access Journals (Sweden)

    Nilvia Esther González García

    2011-06-01

    Full Text Available La leucemia aguda durante el período neonatal es poco frecuente de evolución rápida y pronóstico sombrío. Sus características clínicas y biológicas difieren de las encontradas en niños de mayor edad, y su inicio se caracteriza por afectación cutánea, hepatoesplenomegalia, hiperleucocitosis e infiltración del sistema nervioso central. Se han observado pacientes con formas tanto mieloides como linfoides, pero la leucemia mieloide aguda parece predominar en esta etapa de la vida. Se presenta el caso de un paciente con leucemia congénita clasificada morfológicamente, con aparición de manifestaciones clínicas de enfermedad hematológica desde el nacimiento y diagnóstico de leucemia linfoblástica aguda congénita.Acute leukemia during neonatal period is not frequent, of a fast course and gloomy prognosis. Its clinical and biological features differ of that present in older children and it onset is characterized by cutaneous affection, hepatosplenomegaly, hyperleukocytosis and infiltration of central nervous system (CNS. There are patients presenting with myeloid and lymphoid types, but the acute leukemia seems to predominate in this stage of life. This is the case of a patient with acute leukemia morphologically classified, with appearance of clinical manifestations of hematologic disease from birth and a diagnosis of congenital acute lymphoblastic leukemia.

  19. Flowcytometric Immunophenotypic Profile of Acute Leukemia: Mansoura Experience

    OpenAIRE

    Salem, Dalia A.; Abd El-Aziz, Sherin M.

    2011-01-01

    Acute leukemia (AL) displays characteristic patterns of antigen expression, which facilitate their identification and proper classification. The purpose of this study is to evaluate the diagnostic usefulness of commonly used immune-markers for immunophenotyping of AL and to define the best immune-markers to be used for proper diagnosis and classification of AL. Besides, to recognize the frequency of different AL subtypes and the antigen expression profile in our Egyptian patients. We retrospe...

  20. Elbow septic arthritis associated with pediatric acute leukemia: a case report and literature review.

    Science.gov (United States)

    Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki

    2015-01-01

    Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Diagnosis of acute myeloid leukemia in a dental hospital; report of a ...

    African Journals Online (AJOL)

    2014-10-10

    Oct 10, 2014 ... [1]. Acute myeloid leukemia (AML) can present as leukemic infiltrates in many sites including gingival enlargement, mucosal and skin nodules.[5] Oral lesions occur both in acute and chronic forms of all types of leukemias, however, oral manifestations are more common in the acute stages of the disease.

  3. A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria.

    Science.gov (United States)

    Margolskee, Elizabeth; Mikita, Geoff; Rea, Bryan; Bagg, Adam; Zuo, Zhuang; Sun, Yi; Goswami, Maitrayee; Wang, Sa A; Oak, Jean; Arber, Daniel A; Allen, M Brandon; George, Tracy I; Rogers, Heesun J; Hsi, Eric; Hasserjian, Robert P; Orazi, Attilio

    2018-02-05

    The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid

  4. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    Science.gov (United States)

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-06-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  7. Metaphyseal impaction fractures in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Manson, D.; Cockshott, W.P.; Martin, R.F.

    1989-01-01

    Patients with acute lymphatic leukaemia frequently are osteoporotic. A small subset of these develop disabling metaphyseal transverse fractures, usually bilateral and in the lower limb. These impaction fractures have a characteristic appearance and develop in recently laid down bone. They may develop ab initio of during therapy, Magnesium deficiency is found in these patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  10. Topoisomerase II and leukemia

    Science.gov (United States)

    Pendleton, MaryJean; Lindsey, R. Hunter; Felix, Carolyn A.; Grimwade, David; Osheroff, Neil

    2014-01-01

    Type II topoisomerases are essential enzymes that modulate DNA under- and overwinding, knotting, and tangling. Beyond their critical physiological functions, these enzymes are the targets for some of the most widely prescribed anticancer drugs (topoisomerase II poisons) in clinical use. Topoisomerase II poisons kill cells by increasing levels of covalent enzyme-cleaved DNA complexes that are normal reaction intermediates. Drugs such as etoposide, doxorubicin, and mitoxantrone are frontline therapies for a variety of solid tumors and hematological malignancies. Unfortunately, their use is also associated with the development of specific leukemias. Regimens that include etoposide or doxorubicin are linked to the occurrence of acute myeloid leukemias that feature rearrangements at chromosomal band 11q23. Similar rearrangements are seen in infant leukemias and are associated with gestational diets that are high in naturally occurring topoisomerase II–active compounds. Finally, regimens that include mitoxantrone and epirubicin are linked to acute promyelocytic leukemias that feature t(15;17) rearrangements. The first part of this article will focus on type II topoisomerases and describe the mechanism of enzyme and drug action. The second part will discuss how topoisomerase II poisons trigger chromosomal breaks that lead to leukemia and potential approaches for dissociating the actions of drugs from their leukemogenic potential. PMID:24495080

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Price KE

    2013-08-01

    Full Text Available Kimberly E Price, Najma Saleem, Georgina Lee, Michael SteinbergMassachusetts College of Pharmacy and Health Sciences University, Worcester, MA, USAAbstract: Development of BCR-ABL tyrosine kinase inhibitors (TKIs have improved outcomes for patients diagnosed with chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. However, resistance or intolerance to these TKIs still leaves some patients without many treatment options. One point mutation in particular, the T315I mutation, has been shown to be resistant to first and second generation TKIs. The third generation TKI, ponatinib, may provide an option for these patients. Ponatinib (Iclusig®, an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. A Phase II study evaluated ponatinib in patients who were resistant or intolerant to nilotinib or dasatinib or patients who had the T315I mutation. In the Phase II study, ponatinib produced a major cytogenetic response in 54% of chronic phase chronic myeloid leukemia patients. It further achieved major hematologic response in 52% of patients in the accelerated phase, 31% of patients in the blast phase, and 41% of Philadelphia chromosome positive acute lymphoblastic leukemia patients. Ponatinib also showed efficacy in patients with the T315I mutation. Serious adverse events included arterial thrombosis, hepatotoxicity, cardiovascular risks, pancreatitis, hemorrhage, fluid retention, myelosuppression, rash, abdominal pain, and embryo–fetal toxicity. Due to the risk of these adverse events and potential drug interactions, the use of ponatinib must be carefully weighed against the benefits in treating patients who have limited treatment options.Keywords: BCR-ABL, tyrosine kinase inhibitor, TKI, T315I, Philadelphia chromosome

  13. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  14. The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia.

    Science.gov (United States)

    Balgobind, B V; Zwaan, C M; Pieters, R; Van den Heuvel-Eibrink, M M

    2011-08-01

    Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

  15. Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy

    OpenAIRE

    Mohammad Shahjahani; Elham Khodadi; Mohammad Seghatoleslami; Javad Mohammadi Asl; Neda Golchin; Zeynab Deris Zaieri; Najmaldin Saki

    2015-01-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important diagnostic tools in diagnosis, classification and prognosis in acute myeloid leukemias. Based on World Health Organization (WHO) classification, acute myeloid leukemias can be divided to four groups. Due to...

  16. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial.

    Science.gov (United States)

    Burnett, A K; Hills, R K; Grimwade, D; Jovanovic, J V; Craig, J; McMullin, M F; Kell, J; Wheatley, K; Yin, J A L; Hunter, A; Milligan, D; Russell, N H

    2013-04-01

    Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, PMRC arm. GO did not provide benefit. High white blood cell count (>10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

  17. Data quality in the Danish National Acute Leukemia Registry: A Hematological Data Resource

    DEFF Research Database (Denmark)

    Østgaard, L.S.G.; Nørgaard, J.M.; 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....

  18. Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma

    DEFF Research Database (Denmark)

    Hansen, P B; Kjeldsen, L; Dalhoff, K

    1992-01-01

    Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic...

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

    DEFF Research Database (Denmark)

    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....

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

    DEFF Research Database (Denmark)

    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...

  1. New vessel formation and aberrant VEGF/VEGFR signaling in acute leukemia : Does it matter?

    NARCIS (Netherlands)

    De Bont, ESJM; Neefjes, VME; Rosati, S; Vellenga, E; Kamps, WA

    2002-01-01

    Although many patients with acute leukemia achieve a hematological complete remission with aggressive intensive therapy protocols, a large proportion shows reoccurrence of disease. Novel strategies are warranted. In acute leukemia new vessel formation is observed. New vessel formation is the result

  2. Direct and indirect targeting of MYC to treat acute myeloid leukemia

    OpenAIRE

    Kogan, Scott; Goga, Andrei; Brondfield, S; Brondfield, S; Umesh, S; Umesh, S; Corella, A; Corella, A; Zuber, J; Rappaport, AR; Rappaport, AR; Gaillard, C

    2015-01-01

    © 2015 The Author(s) Purpose: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is often resistant to conventional therapies. The MYC oncogene is commonly overexpressed in AML but has remained an elusive target. We aimed to exami

  3. Diagnosis of acute myeloid leukemia in a dental hospital; report of a ...

    African Journals Online (AJOL)

    Acute myeloid leukemias (AMLs) are aggressive hematopoietic neoplasms that, if untreated, can lead to death within days. Owing to its high morbidity rate, early diagnosis and appropriate medical therapy is essential. Oral lesions may be the presenting feature of acute leukemias and are, therefore, important diagnostic ...

  4. Diagnostic imaging of limbs in children with acute leukemia

    International Nuclear Information System (INIS)

    Song Yingru; Li Chenhui; Li Guo; Ye Wei; Huang Zhongkui; Long Liling; Luo Jianming

    2011-01-01

    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-T 1 WI, SE-T 2 WI and T 2 WI-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 T 1 WI, 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

  5. Increased regulatory T cells in acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Idris, Siti-Zuleha; Hassan, Norfarazieda; Lee, Le-Jie; Md Noor, Sabariah; Osman, Raudhawati; Abdul-Jalil, Marsitah; Nordin, Abdul-Jalil; Abdullah, Maha

    2015-10-01

    Regulation in adaptive immune response balances a fine line that prevents instigation of self-damage or fall into unresponsiveness permitting abnormal cell growth. Mechanisms that keep this balance in check include regulatory T cells (Tregs). Tregs consist of a small but heterogeneous population which may be identified by the phenotype, CD3+CD4+CD25+CD127-. Role of Tregs in pathogenesis of cancers is thus far supported by evidence of increased Tregs in various cancers and may contribute to poorer prognosis. Tregs may also be important in acute leukemias. A review of the literature on Tregs in acute leukemias was conducted and Tregs were determined in B-cell acute lymphoblastic leukemias (ALLs). Studies on Tregs in B-cell ALL are few and controversial. We observed a significantly increased percentage of Tregs (mean ± SD, 9.72 ± 3.79% vs. 7.05 ± 1.74%; P = 0.047) in the bone marrow/peripheral blood of ALL (n = 17) compared to peripheral blood of normal controls (n = 35). A positive trend between Tregs and age (R = 0.474, P = 0.055, n = 17) implicates this factor of poor prognosis in B-cell ALL. Tregs in cancer are particularly significant in immunotherapy. The manipulation of the immune system to treat cancer has for a long time ignored regulatory mechanisms inducible or in place. In lymphoma studies tumor-specific mechanisms that are unlike conventional methods in the induction of Tregs have been hypothesized. In addition, tumor-infiltrating Tregs may present different profiles from peripheral blood pictures. Tregs will continue to be dissected to reveal their mysteries and their impact on clinical significance.

  6. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

  7. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    Science.gov (United States)

    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko

    2015-01-01

    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  8. Comorbidity and performance status in acute myeloid leukemia patients

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; 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 (...... with an increased short- and long-term mortality (adjusted 90 day MR, PS⩾2=3.43 (95%CI=2.30-5.13); adjusted 91 day-3 year MR=1.35 (95%CI=1.06-1.74)). We propose that more patients with comorbidity may benefit from intensive chemotherapy....

  9. Complexity on Acute Myeloid Leukemia mRNA Transcript Variant

    Directory of Open Access Journals (Sweden)

    Carlo Cattani

    2011-01-01

    Full Text Available This paper deals with the sequence analysis of acute myeloid leukemia mRNA. Six transcript variants of mlf1 mRNA, with more than 2000 bps, are analyzed by focusing on the autocorrelation of each distribution. Through the correlation matrix, some patches and similarities are singled out and commented, with respect to similar distributions. The comparison of Kolmogorov fractal dimension will be also given in order to classify the six variants. The existence of a fractal shape, patterns, and symmetries are discussed as well.

  10. Features of children temperament with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    N. A. Kornetov

    2013-01-01

    Full Text Available The temperament characteristics were studied in 86 children with acute lymphoblastic leukemia (ALL at the age of 3–16 years. Research was conducted using standardized and adapted to the Russian-speaking population of parental questionnaires for children of different age groups (Kolpakov V.G. et al., 1993. Statistically significant differences in temperament ALL patients from healthy children installed and feature of temperament, which is most often seen in children with conduct disorder are installed. The need for psychological and/or psychiatric counseling this category of patients is substantiated.

  11. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

    International Nuclear Information System (INIS)

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L.; West, Daniel C.

    2003-01-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  12. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L. [University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States); West, Daniel C. [Department of Pediatrics, University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States)

    2003-02-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  13. Collagen XVIII Mutation in Knobloch Syndrome with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mahajan, Vinit B.; Olney, Ann Haskins; Garrett, Penny; Chary, Ajit; Dragan, Ecaterina; Lerner, Gary; Murray, Jeffrey; Bassuk, Alexander G.

    2010-01-01

    Knobloch syndrome (KNO) is caused by mutations in the collagen XIII gene (COL18A1) and patients develop encephalocele and vitreoretinal degeneration. Here we report an El Salvadorian family where two sisters showed features of KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA sequencing of COL18A1revealed a homozygous, 2-base pair deletion (c3514-3515delCT) in exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic cleavage product endostatin. KNO patients with mutations in COL18A1 may be at risk for endostatin-related conditions including malignancy. PMID:20799329

  14. NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017.

    Science.gov (United States)

    Brown, Patrick A; Shah, Bijal; Fathi, Amir; Wieduwilt, Matthew; Advani, Anjali; Aoun, Patricia; Barta, Stefan K; Boyer, Michael W; Bryan, Teresa; Burke, Patrick W; Cassaday, Ryan; Coccia, Peter F; Coutre, Steven E; Damon, Lloyd E; DeAngelo, Daniel J; Frankfurt, Olga; Greer, John P; Kantarjian, Hagop M; Klisovic, Rebecca B; Kupfer, Gary; Litzow, Mark; Liu, Arthur; Mattison, Ryan; Park, Jae; Rubnitz, Jeffrey; Saad, Ayman; Uy, Geoffrey L; Wang, Eunice S; Gregory, Kristina M; Ogba, Ndiya

    2017-09-01

    The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management. Copyright © 2017 by the National Comprehensive Cancer Network.

  15. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  16. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2018-01-01

    . PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483......BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival...... to improve survival in relapsed childhood ALL....

  17. Technical relapsed testicular irradiation for acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-01-01

    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.

  18. Genital Infection as a First Sign of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Naoki Oiso

    2010-02-01

    Full Text Available Fournier’s gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier’s gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy.

  19. Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia

    OpenAIRE

    Hou, Qianqian; Liao, Fei; Zhang, Shouyue; Zhang, Duyu; Zhang, Yan; Zhou, Xueyan; Xia, Xuyang; Ye, Yuanxin; Yang, Hanshuo; Li, Zhaozhi; Wang, Leiming; Wang, Xi; Ma, Zhigui; Zhu, Yiping; Ouyang, Liang

    2017-01-01

    GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene...

  20. Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

    Science.gov (United States)

    Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

    2014-05-01

    Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

  1. Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors

    Science.gov (United States)

    Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

    2012-01-01

    Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

  2. Acute interstitial nephritis in T-cell leukemia in a pediatric patient.

    Science.gov (United States)

    Biro, Erika; Szikszay, Edit; Pethő-Orosz, Petronella; Bigida, László; Balla, György; Szabó, Tamás

    2016-09-01

    Acute lymphoid leukemia is the most frequently occurring malignancy in childhood, but acute tubulointerstitial nephritis with associated acute renal failure as the leading manifestation of leukemia is extremely rare. Only a few pediatric cases have been described in the literature. We present a surprising case in which physical examination and initial investigation were not typical for leukemia. Ultrasound showed only modest kidney enlargement while laboratory results indicated acute renal failure. Renal biopsy indicated tubulointerstitial nephritis, and subsequent steroid treatment led to sudden clinical improvement. One month later, however, the patient returned with typical clinical features of leukemia. Re-evaluation of the original kidney biopsy block indicated T-cell acute lymphoid leukemia. The present case highlights the importance of renal biopsy. © 2016 Japan Pediatric Society.

  3. A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia.

    Science.gov (United States)

    Hale, Victoria; Hale, Gregory A; Brown, Patrick A; Amankwah, Ernest K

    2017-01-01

    Acute leukemia is the most common childhood cancer diagnosis and leading cause of cancer-related death among children and adolescents. Despite substantial improvements in the survival rate of childhood acute leukemia, approximately 20-40% of the patients who undergo treatment develop relapse, with a dismal one third of these patients surviving in the long term. Epigenetics plays an important role in the progression of cancer, and existing evidence suggests a role in childhood acute leukemia relapse. A better understanding of the epigenetic mechanisms in recurrent acute leukemia could potentially lead to novel therapeutic regimens to prevent or treat disease recurrences. In this review, we summarize existing evidence on two of the most studied epigenetic mechanisms, DNA methylation and microRNA expression, in recurrent pediatric acute leukemia. © 2016 S. Karger AG, Basel.

  4. [Myeloid/natural killer cell precursor and myeloid/natural killer cell acute leukemia].

    Science.gov (United States)

    Ni, Ming; Chen, Bao-An

    2014-04-01

    With the popularity of flow cytometry, the classification of leukemia become more detailed. Myeloid/natural killer cell precursor acute leukemia and myeloid/natural killer cell acute leukemias are generally recognized as two kinds of rare leukemias and have poor prognosis. The cells expressed both myeloid and lymphatic antigens in these two leukemia and can not be diagnosed by morphology. The only basis to make a definite diagnosis is their unique Immunophenotyping. The role of CD7 and CD56 in these two leukemia are compelling, in the other hand, as the progress of cell differentiation research, there are many new awareness of NK cell differentiation. In this article, the biological origin, clinical manifestation, diagnosis, treatment and the role of CD7 and CD56 in these two leukemia are briefly summarized.

  5. From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia.

    Science.gov (United States)

    Chen, Sai-Juan; Zhou, Guang-Biao; Zhang, Xiao-Wei; Mao, Jian-Hua; de Thé, Hugues; Chen, Zhu

    2011-06-16

    Arsenic had been used in treating malignancies from the 18th to mid-20th century. In the past 3 decades, arsenic was revived and shown to be able to induce complete remission and to achieve, when combined with all-trans retinoic acid and chemotherapy, a 5-year overall survival of 90% in patients with acute promyelocytic leukemia driven by the t(15;17) translocation-generated promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion. Molecularly, arsenic binds thiol residues and induces the formation of reactive oxygen species, thus affecting numerous signaling pathways. Interestingly, arsenic directly binds the C3HC4 zinc finger motif in the RBCC domain of PML and PML-RARα, induces their homodimerization and multimerization, and enhances their interaction with the SUMO E2 conjugase Ubc9, facilitating subsequent sumoylation/ubiquitination and proteasomal degradation. Arsenic-caused intermolecular disulfide formation in PML also contributes to PML-multimerization. All-trans retinoic acid, which targets PML-RARα for degradation through its RARα moiety, synergizes with arsenic in eliminating leukemia-initiating cells. Arsenic perturbs a number of proteins involved in other hematologic malignancies, including chronic myeloid leukemia and adult T-cell leukemia/lymphoma, whereby it may bring new therapeutic benefits. The successful revival of arsenic in acute promyelocytic leukemia, together with modern mechanistic studies, has thus allowed a new paradigm to emerge in translational medicine.

  6. The Biology and Targeting of FLT3 in Pediatric Leukemia

    Science.gov (United States)

    Annesley, Colleen E.; Brown, Patrick

    2014-01-01

    Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high-risk groups of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), as well as for relapsed leukemia, remains poor. Intensification of chemotherapy regimens for those at highest risk has improved success rates, but at the cost of significantly increased morbidity and long-term adverse effects. With the success of imatinib in Philadelphia-chromosome-positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over recent years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3). FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high-risk pediatric AML and in certain high-risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy. PMID:25295230

  7. Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients.

    Science.gov (United States)

    Colovic, Milica; Colovic, Natasa; Radojkovic, Milica; Stanisavljevic, Dejana; Kraguljac, Nada; Jankovic, Gradimir; Tomin, Dragica; Suvajdzic, Nada; Vidovic, Ana; Atkinson, Henry Dushan

    2012-09-01

    A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0

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

    Science.gov (United States)

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

    2016-01-01

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

  9. [The expression and clinical significance of miR-203 in pediatric acute leukemia].

    Science.gov (United States)

    Wang, Na; Pan, Jian; Cao, Lan; Lu, Jun; Xiao, Pei-fang; Zhao, Wen-li; Hu, Shao-yan; Chai, Yi-huan

    2013-09-01

    To investigate the methylation, expression and clinical significance of miR-203 in pediatric acute leukemia. The methylation status of miR-203 promoter CpG islands was detected with methylation-specific polymerase chain reaction. The expression of miR-203 was detected by Taqman real- time quantitative polymerase chain reaction. And the clinical significance of miR-203 in pediatric acute leukemia (ALL) was also analyzed. The promoter of miR-203 was unmethylated in all of 31 pediatric acute lymphoblastic leukemia, all of 15 pediatric acute myeloid leukemia (AML) and all of 23 controls. The relative expression levels of miR-203 in controls, pediatric acute leukemia, ALL and AML were 16.93±6.31, 48.97±10.38, 55.88±12.91, 24.28±9.10 respectively. The results indicated that miR-203 was significantly up- regulated in pediatric acute leukemia (P=0.011) and ALL (P=0.009), not in pediatric AML (P=0.514) compared with control. The expression of miR-203 was significantly related with the gender, immunophenotype, chromosome, fusion gene, BCR-ABL, SIL-TAL1 and prednisone experiment in pediatric ALL and the gender, chromosome, fusion gene, SIL-TAL1 in pediatric acute leukemia (Ppediatric acute leukemia. miR- 203 may be a protooncogene involved in the formation of pediatric acute leukemia and ALL. Further analyses indicated that high expression of miR-203 may be associated with poor prognosis of pediatric ALL and acute leukemia.

  10. Cytotoxic effect of Spirulina platensis extracts on human acute leukemia Kasumi-1 and chronic myelogenous leukemia K-562 cell lines

    OpenAIRE

    Flores Hernandez, Flor Yohana; Khandual, Sanghamitra; Ramírez López, Inocencia Guadalupe

    2017-01-01

    Objective: To evaluate the cytotoxic effects of Spirulina platensis extracts on acute leukemia Kasumi-1 and chronic leukemia K-562 cancer cell lines. Methods: Various concentrations of Spirulina platensis extracts (0.25–50.00 mg/mL) obtained with different solvents were used to treat cell lines for 72 h. For cytotoxic effect studies, cell viability test with trypan blue solution, MTT assay and microscopic cytomorphological assessment were done. Results: Spirulina extract obtained with 7...

  11. ACUTE MYELOGENOUS LEUKEMIA PRESENTING WITH ABRUPT ONSET LEUKEMIA CUTIS IN A YOUNG BOY: A RARE CASE REPORT

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    Lohit Kumar

    2015-05-01

    Full Text Available We report an 25 - year - old young male patient who presented with sudden onset multiple generalized skin lesions of dusky erythematous plaques of various size and shape all over the body which tends to bleed on rubbing. Histological evaluation revealed leukemia cutis wit h underlying atypical infiltrate contained atypical myeloid forms consistent with acute myelogenous leukemia (AML. His skin biopsy provided the first evidence of progression to AML. AML presenting with sudden onset leukemia cutis in a young boy is an extr emely rare entity

  12. Cranial irradiation in acute leukemia: dose estimate in the lens

    International Nuclear Information System (INIS)

    Kline, R.W.; Gillin, M.T.; Kun, L.E.

    1979-01-01

    Cranial irradiation for subclinical arachnoid infiltration is standard treatment in childhood acute lymphocytic leukemia. The incidental dose received by the ocular lens is of potential importance since these children evidence a significant long-term survival rate. Comparison of the lens dose using 6MV and 4MV photon beams and a cobalt unit is presented in terms of ion chamber measurements in a water phantom and thermo-luminescent dosimetry (TLD) measurements in a head phantom. TLD measurements on patients treated for acute lymphocytic leukemia (ALL) are examined and used to estimate the dose to the lens. It is demonstrated that the dose to the lens depends strongly on the choice of field margin and on the daily patient set-up. However, using parallel opposed beams in a clinically determined optimal set-up, the dose to the lens is approximately 20 to 30% of the midline central axis dose. By angling the treatment head to eliminate the geometrical divergence of the beam, it is possible to reduce the lens dose to approximately 15% of the midline dose

  13. Surrogate marker profiles for genetic lesions in acute leukemias.

    Science.gov (United States)

    Paietta, Elisabeth

    2010-09-01

    The basic hypothesis of surrogate marker profiles is that individual genetic lesions result in characteristic distortions of the cellular phenotype with some predictable consistency that can be exploited by sophisticated immunophenotyping. While cytogenetic and molecular aberrancies currently are accepted prognostic predictors in acute leukemias, single antigen expression and even antigenic profiles rarely impact on prognosis. However, increasingly, phenotypes are delineated which can serve as surrogates for underlying genetic aberrations of clinical importance. This development is of particular significance as antileukemic therapy becomes available that targets any component of the disturbed molecular pathways associated with these genetic lesions. This chapter will focus on established surrogate marker profiles, such as those for PML/RARα, AML1/ETO, FLT3-gene mutated acute lymphocytic leukemia (ALL), and BCR/ABL(POS) ALL. As the list of therapeutic targets grows, the role of surrogate antigen profiles will grow, as they can predict for the efficacy of targeted approaches in lieu of expensive, time-consuming and not always accessible genetic analyses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

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    Yunbao Pan

    2017-06-01

    Full Text Available Acute myeloid leukemia (AML is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

  15. First-line treatment of acute lymphoblastic leukemia with pegasparaginase

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    Riccardo Masetti

    2009-07-01

    Full Text Available Riccardo Masetti, Andrea PessionPediatric Oncology and Hematology Unit “Lalla Seràgnoli”, University of Bologna, Bologna, ItalyAbstract: Acute lymphoblastic leukemia (ALL accounts for almost 4000 cases annually in the United States, approximately two thirds of which are in children and adolescents. Treatment results of ALL have improved considerably in the past decade, due to an optimal stratification of patients and a rational use of different antileukemic agents among which L-asparaginase (L-ASNase plays a fundamental role. This drug has been used in pediatric ALL chemotherapy protocols for almost 3 decades. In the 1970s and 1980s a chemically modified form of this enzyme called pegasparaginase (PEG-ASNase was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. The different advantages of PEG-ASNase have been demonstrated in many clinical studies, the last of which underline the utility of this drug in front-line therapy of ALL. In this review, we discuss the pharmacological advantages and clinical potential of PEG-ASNase and its important use in first-line treatment of ALL.Keywords: pegasparaginase, acute, lymphoblastic leukemia, pegylation

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

    Science.gov (United States)

    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.

  17. Acute Myeloid Leukemia: Clinical Spectrum of 125 Patients.

    Science.gov (United States)

    Sultan, Sadia; Zaheer, Hasan Abbas; Irfan, Syed Mohammed; Ashar, Sana

    2016-01-01

    Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1).

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

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    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.

  19. Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia.

    Science.gov (United States)

    De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Grieco, Vitina; Bianchino, Gabriella; Nozza, Filomena; Campia, Valentina; D'Alessio, Francesca; La Rocca, Francesco; Caivano, Antonella; Villani, Oreste; Cilloni, Daniela; Musto, Pellegrino; Del Vecchio, Luigi

    2017-06-01

    Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in 'AML with maturation' (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition.

  20. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells*

    Science.gov (United States)

    Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas; Fiser, Karel; Hrusak, Ondrej; Lund-Johansen, Fridtjof

    2016-01-01

    Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients. To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation. In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified

  1. Immunological Subtypes of Acute Lymphoblastic Leukemia- Beyond Morphology: Experience from Kidwai State Cancer Institute, Bengaluru, India.

    Science.gov (United States)

    Rajkumar, Namrata N; Vijay, Raghavendra H

    2017-07-01

    Acute lymphoblastic leukemia (ALL) is disease of lymphoid precursors and is the most common cancer. Diagnosis of ALL is made by evaluating morphology and flowcytometric Immunophenotyping (FCI)and is an important adjunct in diagnosis and determining treatment in ALL, with availability of extensive monoclonal antibodies in the recent years there is tremendous progress in the field of FCI, and is a requirement by World Health Organisation for the classification of acute lymphoblastic Leukemia. Flow cytometric immunophenotyping of the leukemic blasts helps in categorization of acute lymphoblastic leukemia as B-ALL or T-ALL. Though ALL is the most common cancer, there is paucity of study in Indian scenario, and very few reports of immunologically subtyping of ALL is reported. To confirm the clinical/morphological diagnosis and to determine immunological subtype of acute lymphoblastic leukemia as per requirement by World Health Organization for the classification of acute lymphoblastic leukemia. At Kidwai State Cancer institute, Bangalore, we have performed of Immunophenotyping in 1425 untreated cases of acute leukemias during January 2012 - August 2015. Flow cytometry analysis of 1425 cases of acute Leukemias were performed, 918 (64.42%) were acute lymphoblastic Leukemia, 688 were B-ALL (74.94%), majority(480) of B-ALL were in children (69.76%), 230 were T-ALL (25.05 %), B-ALL was the most common subtype of acute leukemias. Acute lymphoblastic leukemia is the most common leukemia in adults and children. Immunophenotping helps in confirming the clinical/morphological diagnosis and in determining the immunological subtype of acute lymphoblastic leukemia, thus has an important role in deciding on the treatment regime. ALL is the disease of lymphoid precursors and is more common cancer in children than adults. B-ALL was the most common subtype of acute leukemias both in adults and in children. T-ALL is less common in pediatric population. Flowcytometric techniques are used

  2. A 78-year-old man with acute myeloid leukemia (AML) and acute renal failure.

    Science.gov (United States)

    Tapper, Elliot B; Luptakova, Katarina; Joyce, Robin M; Tzachanis, Dimitrios

    2014-08-30

    Male, 78. Acute myeloid leukemia (AML). Dyspnea • fatigue. Idarubicin followed by cytarabine. Chemotherapy. Hematology. Unusual clinical course. Renal failure is a common presentation of acute myelomonocytic and monocytic leukemia. It is usually the result of a combined glomerular and tubular dysfunction and is associated with a poor prognosis. No guidelines exist for treatment. We herein describe the case of a 78-year-old Caucasian man who presented with acute myeloid leukemia M5, leukostasis with a white count of 340 000/ml, and acute renal failure with a creatinine of 7.7/dL. The patient was initially treated with leukapheresis and 3 days of idarubicin in the setting of continuous renal replacement therapy that resulted in rapid reversal of his renal failure. He then received 7 days of continuous infusion cytarabine and went into a complete remission. Renal failure may complicate the presentation of AML but can be reversible with treatment. Dose adjustment of the chemotherapy is not needed and the treatment can be greatly facilitated with the use of continuous renal replacement therapy, as indicated in our case report. In addition, we emphasize that organ dysfunction, even in elderly patients, is not necessarily a contraindication to aggressive treatment if it is felt to be disease-related and reversible.

  3. Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review.

    Science.gov (United States)

    Lam, Grace Kee See; Leung, Alex Wing Kwan; Ha, Shau Yin; Luk, Chung Wing; Li, Chak Ho; Ling, Siu Cheung; Chiang, Alan Kwok Shing; Li, Chi Kong

    2016-03-01

    Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  5. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  6. Role of FAB classification of acute leukemias in era of immunophenotyping.

    Science.gov (United States)

    Sachdeva, Man Updesh Singh; Ahluwalia, Jasmina; Das, Reena; Varma, Neelam; Garewal, G

    2006-10-01

    French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.

  7. Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization.

    Science.gov (United States)

    Heesch, Sandra; Neumann, Martin; Schwartz, Stefan; Bartram, Isabelle; Schlee, Cornelia; Burmeister, Thomas; Hänel, Matthias; Ganser, Arnold; Heuser, Michael; Wendtner, Clemens-Martin; Berdel, Wolfgang E; Gökbuget, Nicola; Hoelzer, Dieter; Hofmann, Wolf-Karsten; Thiel, Eckhard; Baldus, Claudia D

    2013-06-01

    Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.

  8. [Research progress on cellular and molecular genetics of acute non-lymphocytic leukemia].

    Science.gov (United States)

    Xiong, Wen-Yan; Tu, San-Fang; Lu, Zhi-Gang; Li, Yu-Hua

    2010-04-01

    With the extensive application of cellular and molecular genetic techniques in the research of acute leukemia (AL), the diagnosis of AL type has been developed from FAB typing which was based on morphological classification in 1976 to MICM typing in 2001. This progress highlights the importance of cellular and molecular genetic changes in the diagnosis of leukemia. The cellular and molecular genetic abnormalities in acute leukemia can make the stratification of risk and give the guidance for prognosis and treatment, which is also critical for the development of new drugs. This article has focused on chromosomal abnormalities, fusion gene expression and their relationship with the leukemia diagnosis, prognosis and treatment. This article is also a concise review on several common gene mutations in cytogenetics of ANLL for the assessment of disease prognosis. In recent years, further exploration of molecular cytogenetic mechanisms of various types of leukemia in ANLL contributed to the development of new therapeutic strategy for leukemia.

  9. Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Ito, Shoko; Fujiwara, Shin-Ichiro; Mashima, Kiyomi; Umino, Kento; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-05-01

    The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

  10. CD117 expression on blast cells in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    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.

  11. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  12. Textural characteristics of bone marrow blast nucleus images with different variants of acute lymphoblastic leukemia

    Science.gov (United States)

    Nikitaev, V. G.; Pronichev, A. N.; Polyakov, E. V.; Mozhenkova, A. V.; Tupitsin, N. N.; Frenkel, M. A.

    2018-01-01

    The paper describes the method of recognition of T - and B - variants of acute lymphoblastic leukemia in microscopic images of blood cells. The method is based on the use of texture characteristics of images. Experimental recognition accuracy evaluation is obtained from the sample of 38 patients (17 with T-ALL and 21 with B-ALL variants of acute lymphoblastic leukemia). The obtained results show the possibility of applying of the proposed approach to the differential diagnosis of T- and B- variants of acute lymphoblastic leukemia.

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

    International Nuclear Information System (INIS)

    Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

    1980-01-01

    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. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    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.

  15. Coagulation Profile at Diagnosis in Patients with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sehgal, Shivali; Sharma, Sunita; Chandra, Jagdish; Nangia, Anita

    2016-10-01

    To evaluate the coagulation parameters at the time of diagnosis in pediatric acute lymphoblastic leukemia (ALL) patients. A total of 65 newly diagnosed ALL patients upto 18 y of age along with 30 age and sex matched controls were included in the study. Coagulation tests including Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (FBG) assay, D-dimer (D-DI) assay, Coagulation inhibitor levels and tests for fibrinolysis were performed. At baseline, APTT of the patients was significantly prolonged (p 0.033), but PT and fibrinogen were comparable in the two groups. Protein C (PC) and Protein S (PS) were both significantly reduced in the cases, while antithrombin was comparable to control values (p DI levels were significantly high (p < 0.001). The onset of leukemia is associated with hemostatic derangement favouring hypercoagulability. The coagulopathy is due to thrombin activation (as evidenced by raised d-dimer). The decreased fibrinolysis (due to reduced tPA and raised PAI-1) and low levels of PC and PS contribute to the hypercoagulable state at the time of diagnosis.

  16. Karyotype complexity and prognosis in acute myeloid leukemia.

    Science.gov (United States)

    Stölzel, F; Mohr, B; Kramer, M; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; Stuhlmann, R; Einsele, H; Krause, S W; Serve, H; Hänel, M; Herbst, R; Neubauer, A; Sohlbach, K; Mayer, J; Middeke, J M; Platzbecker, U; Schaich, M; Krämer, A; Röllig, C; Schetelig, J; Bornhäuser, M; Ehninger, G

    2016-01-15

    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 in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.

  17. Recent developments in immunotherapy of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Felix S. Lichtenegger

    2017-07-01

    Full Text Available Abstract The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years. Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1 antibody-drug conjugates, (2 T cell-recruiting antibody constructs, (3 chimeric antigen receptor (CAR T cells, (4 checkpoint inhibitors, and (5 dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results. While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts.

  18. Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Hou, Qianqian; Liao, Fei; Zhang, Shouyue; Zhang, Duyu; Zhang, Yan; Zhou, Xueyan; Xia, Xuyang; Ye, Yuanxin; Yang, Hanshuo; Li, Zhaozhi; Wang, Leiming; Wang, Xi; Ma, Zhigui; Zhu, Yiping; Ouyang, Liang; Wang, Yuelan; Zhang, Hui; Yang, Li; Xu, Heng; Shu, Yang

    2017-05-30

    GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL patients, 173 candidates were identified to be significantly associated with GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit tissue-specific and subtype-specific association with GATA3. Through overexpression and down-regulation of GATA3 in leukemia cell lines, several reported and novel GATA3 regulated genes were validated. Moreover, association of GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation.

  19. The Association of Viral Infection and Acute Leukemia in Childhood: Two Case Reports

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    Murat Söker

    2005-01-01

    Full Text Available Hepatitis A and Measles are the most common viral infection in pediatric patients. Viral infections causes to serious problem in immunocompromised patients such as acute leukemias. It is known that some viral infection agent causes hematologic malignancies. We report here two patient with acute leukemias who admitted to our clinic with similar to viral infection. The first case is a patient with acute lymphoblastic leukemia (ALL presented with ascites and pleural effusion. In this patient, the major clinical problem is hepatitis A. The second case is a patient with ALL who admitted with symptoms of measles. We discussed here, some viral infections may cause to leukemia and those may be associated with leukemias.

  20. Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

    International Nuclear Information System (INIS)

    Vaughan, W.P.; Karp, J.E.; Burke, P.J.

    1983-01-01

    Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

  1. [Treatment of acute myeloid leukemia -- a single center experience (2007-2013)].

    Science.gov (United States)

    Selmeczi, Anna; Udvardy, Miklós; Illés, Arpád; Telek, Béla; Kiss, Attila; Batár, Péter; Reményi, Gyula; Szász, Róbert; Ujj, Zsófia; Márton, Adrienn; Ujfalusi, Anikó; Hevessy, Zsuzsanna; Pinczés, László; Bedekovics, Judit; Rejtő, László

    2014-04-27

    Mortality of acute myeloid leukemia is still 60-70% in young (myeloid leukemia. From 2007 to 2013, 173 patients with acute myeloid leukemia were treated. Patients were classified according to the European LeukemiaNet prognostic guideline. Association between mortality and the type of acute myeloid leukemia (secondary or primary), dose of daunoblastin at induction of treatment, and the rate of minimal residual disease were investigated. The 5-year survival probability was 25% in young adults and 2% in the elderly. The survival was significantly influenced by these prognostic factors. The 5-year survival rate was 50% in the young, favorable prognostic group. The 90 mg/m2 daunoblastin dose was found to be beneficial. Addition of bortezomib to the standard induction protocol had an additional beneficial effect. The speed and depth of the response to induction therapy, and the initial white blood cell count had an apparent effect on survival.

  2. Proteomic analysis of human acute leukemia cells: insight into their classification.

    Science.gov (United States)

    Cui, Jiu-Wei; Wang, Jie; He, Kun; Jin, Bao-Feng; Wang, Hong-Xia; Li, Wei; Kang, Li-Hua; Hu, Mei-Ru; Li, Hui-Yan; Yu, Ming; Shen, Bei-Fen; Wang, Guan-Jun; Zhang, Xue-Min

    2004-10-15

    French-American-British (FAB) classification of acute leukemia with genetic heterogeneity is important for treatment and prognosis. However, the distinct protein profiles that contribute to the subtypes and facilitate molecular definition of acute leukemia classification are still unclear. The proteins of leukemic cells from 61 cases of acute leukemia characterized by FAB classification were separated by two-dimensional electrophoresis, and the differentially expressed protein spots were identified by both matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS). The distinct protein profiles of acute leukemia FAB types or subtypes were successfully explored, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5) and acute lymphoid leukemia (ALL), which were homogeneous within substantial samples of the respective subgroups but clearly differed from all other subgroups. We found a group of proteins that were highly expressed in M2 and M3, rather than other subtypes. Among them, myeloid-related proteins 8 and 14 were first reported to mark AML differentiation and to differentiate AML from ALL. Heat shock 27 kDa protein 1 and other proteins that are highly expressed in ALL may play important roles in clinically distinguishing AML from ALL. Another set of proteins up-regulated was restricted to granulocytic lineage leukemia. High-level expression of NM23-H1 was found in all but the M3a subtype, with favorable prognosis. These data have implications in delineating the pathways of aberrant gene expression underlying the pathogenesis of acute leukemia and could facilitate molecular definition of FAB classification. The extension of the present analysis to currently less well-defined acute leukemias will identify additional subgroups.

  3. Allelic Imbalances in Radiation—Associated Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Rosemann

    2011-05-01

    Full Text Available Acute myeloid leukemia (AML can develop as a secondary malignancy following radiotherapy, but also following low-dose environmental or occupational radiation exposure. Therapy-related AML frequently carries deletions of chromosome 5q and/or 7, but for low-dose exposure associated AML this has not been described. For the present study we performed genome-wide screens for loss-of-heterozygosity (LOH in a set of 19 AML cases that developed after radiation-exposure following the Chernobyl accident. Using Affymetrix SNP arrays we found large regions of LOH in 16 of the cases. Eight cases (42% demonstrated LOH at 5q and/or 7, which is a known marker of complex karyotypic changes and poor prognosis. We could show here for the first time that exposure to low-dose ionizing radiation induces AML with molecular alterations similar to those seen in therapy-related cases.

  4. Biology and relevance of human acute myeloid leukemia stem cells.

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2017-03-23

    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  5. Treatment of Young Adults with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kansagra, Ankit; Litzow, Mark

    2017-06-01

    Young adults with acute lymphoblastic leukemia are a distinctive category of patients, with substantial difference in disease biology and response to therapy; hence, they pose unique challenges and issues beyond those faced by children and older adults. Despite inferior survival compared to children, there is growing evidence to suggest that young adults have improved outcomes when treated with pediatric-based approaches. With better supportive care and toxicity management and multidisciplinary team and approach, we have made great improvement in outcomes of young adults with ALL. However, despite significant progress, patients with persistence of minimal residual disease have a poor prognosis. This review discusses current controversies in the management of young adults with ALL, outcomes following pediatric and adult protocols, and the role of allogeneic stem cell transplantation. We also explore recent advances in disease monitoring and highlight our approach to incorporation of novel therapies in the management of young adults with ALL.

  6. Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Nardi, Valentina; Hasserjian, Robert P

    2016-03-01

    Cytogenetic analysis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. Mutational analysis of certain genes, such as SF3B1, is also becoming an important tool to distinguish subsets of MDS that have different biologic behaviors. It is still uncertain how to optimally combine karyotype with mutation data in diagnosis and risk-stratification of AML and MDS, particularly in cases with multiple mutations and/or several mutationally distinct subclones. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-01-01

    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

  8. [Diagnostics, classification and prognostic criteria of acute myeloid leukemia].

    Science.gov (United States)

    Heilmeier, Bernhard; Buske, Christian; Spiekermann, Karsten; Bohlander, Stefan; Feuring-Buske, Michaela; Hiddemann, Wolfgang; Braess, Jan

    2007-04-15

    The continuously growing knowledge about criteria important for biology, pathogenesis, prognosis and treatment of acute myeloid leukemia (AML) necessitates a broad spectrum of diagnostic methods for first diagnosis and for the further course of the disease. Relevant diagnostic techniques (cytomorphology with cytochemistry, immunophenotyping, cytogenetics and molecular genetics, DNA array) are described - with a focus on their mode of operation as well on their clinical significance. Due to the high clinical relevance and growing complexity, AML diagnostics should be performed in specialized laboratories. Compared to the FAB classification which is based primarily on morphological criteria, the classification recommended in 2001 by the WHO additionally takes cytogenetics, molecular genetics and further clinical factors into consideration. Both classifications are described. A wide range of prognostic criteria of AML is discussed on the basis of currently available clinical data. The most important criteria are the karyotype of the leukemic clone and the patient's age.

  9. Myeloperoxidase index and subtypes of acute myeloid leukemia.

    Science.gov (United States)

    Eivazi-Ziaei, Jamal

    2009-06-01

    Acute myeloid leukemia (AML) should be classified into subtypes according to the French-American-British (FAB) or, preferably, the newer World Health Organization (WHO) classification schemes. FAB is purely a morphological classification. It does not determine treatment (except M3) or prognosis for the patient which requires cytogenetics. Haematological analyzer had been used for classification of leukaemia in several studies. Neutrophil myeloperoxidase activity (MPXI) can be performed by Technicon H1 (Bayer) automated cell counter. The aim of this study was the statement of myeloperoxidase index and subgroups of AML. In the study of medical records of 72 patients with AML from 2006-7, we found that MPXI was negative in M4 and M5 while 75% of M3 cases had high MPXI values. MPXI level may help to differentiate subtypes of AML.

  10. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    Science.gov (United States)

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-09

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

    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......--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets...... that dominate in the first 5-7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on pre-existing preleukemic cells Udgivelsesdato: 2008/12...

  12. Study on subsequent neurologic complications in children with acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Naoaki; Shimazaki, Haruyo; Hoshi, Yasutaka; Akatsuka, Jun-ichi (Jikei Univ., Tokyo (Japan). School of Medicine)

    1989-06-01

    Twenty-seven children with acute leukemia were studied in order to detect the subsequent neurologic complications due to chemotherapy and radiation therapy. Twenty-four patients with ALL received central nervous system prophylaxis including cranial irradiation. The methods of evaluation consisted of electroencephalogram (EEG), computed tomography of the head (CT scan), soft neurological sign, intelligence quotient (IQ) and Bender Gestalt test. The patients with relapse showed severe abnormalities in various kinds of examinations. Younger children at diagnosis were associated with a higher abnormality rate of soft neurological signs and Bender Gestalt test. Factors which were found to be closely associated with a lower IQ score included younger children at diagnosis and longer duration of remission time. These results indicate the need for caution for the dosage of cranial irradiation for younger patients in CNS prophylaxis, and improvement of a lower IQ score in long-term survivors requires further investigation as to the appropriate intellectual environment for their development after remission. (author).

  13. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  15. An integrative scoring system for survival prediction following umbilical cord blood transplantation in acute leukemia

    NARCIS (Netherlands)

    Shouval, Roni; Ruggeri, Annalisa; Labopin, Myriam; Mohty, Mohamad; Sanz, Guillermo; Michel, Gerard; Kuball, Jürgen; Chevallier, Patrice; Al-Seraihy, Amal; Milpied, Noel Jean; De Heredia, Cristina Diaz; Arcese, William; Blaise, Didier; Rocha, Vanderson; Fein, Joshua; Unger, Ron; Baron, Frederic; Bader, Peter; Gluckman, Eliane; Nagler, Arnon

    2017-01-01

    Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free

  16. A comparison of surface marker analysis and FAB classification in acute myeloid leukemia

    NARCIS (Netherlands)

    van der Reijden, H. J.; van Rhenen, D. J.; Lansdorp, P. M.; van't Veer, M. B.; Langenhuijsen, M. M.; Engelfriet, C. P.; von dem Borne, A. E.

    1983-01-01

    Surface marker analysis with rosette tests and a large panel of xenoantisera and monoclonal antibodies was done on the malignant cells of 55 patients with acute myeloid leukemia (AML). The diagnosis was made on morphological and cytochemical grounds, and the leukemias were classified according to

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

    Directory of Open Access Journals (Sweden)

    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

  18. Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Tim D.D. Somerville

    2018-01-01

    Full Text Available The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML, ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.

  19. DNA methylation changes are a late event in acute promyelocytic leukemia and coincide with loss of transcription factor binding

    DEFF Research Database (Denmark)

    Schoofs, Till; Rohde, Christian; Hebestreit, Katja

    2013-01-01

    . Transcription factor-binding sites (eg, the c-myc-binding sites) were associated with low methylation. However, SUZ12- and REST-binding sites identified in embryonic stem cells were preferentially DNA hypermethylated in APL cells. Unexpectedly, PML-RARα-binding sites were also protected from aberrant DNA...

  20. [Effect of CDK Inhibitor LS-007 on Acute Lymphoblastic Leukemia and Its Mechanism].

    Science.gov (United States)

    Lu, Jiang-Feng; Xu, Feng-Ling; Lu, Jun; Ren, Yu-Guo

    2017-04-01

    To study the effect of cyclin dependent kinase(CDK) inhibitor LS-007 on acute lymphoblastic leukemia and its mechanism. The acute lymphocytic leukemia cell line was cultured and treated by LS-007, flavopiridol and ABT-199, then the changes of apoptosis-related factor mRNA and protein levels were detected by using mRNA quantitative PCR and Werstern blot. quantitative PCR and Western blot detection showed that the levels of antiapoptotic protein decreased significantly in acute lymphoblastic leukemia cells after LS-007 treatment, and the pro-apoptotic effect of LS-007 combined with ABT-199 was much better. LS-007 can affect the phosphorylation of RNA polymerase sites and promote cell apoptosis through changing the activities of CDK, thus having some positive significance for relieving acute lymphoblastic leukemia.

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

    International Nuclear Information System (INIS)

    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. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2003-01-01

    textabstractResistance of leukemic cells to chemotherapeutic agents is associated with an unfavorable outcome in pediatric acute lymphoblastic leukemia (ALL). To investigate the underlying mechanisms of cellular drug resistance, the activation of various apoptotic parameters in

  4. Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma

    Science.gov (United States)

    2018-03-01

    Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia

  5. Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers

    DEFF Research Database (Denmark)

    Nielsen, Stine N.; Eriksson, Frank; Rosthoej, Susanne

    2017-01-01

    BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology...

  6. DNA copy number analysis from mice with radiation-induced acute myeloid leukemia

    Data.gov (United States)

    National Aeronautics and Space Administration — Certain mouse strains such as CBA C3H and RFM have high incidence of radiation-induced acute myeloid leukemia (AML). The data in this series wer generated by using...

  7. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the

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

    DEFF Research Database (Denmark)

    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....

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

    NARCIS (Netherlands)

    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

  10. High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias.

    Science.gov (United States)

    Morisot, S; Wayne, A S; Bohana-Kashtan, O; Kaplan, I M; Gocke, C D; Hildreth, R; Stetler-Stevenson, M; Walker, R L; Davis, S; Meltzer, P S; Wheelan, S J; Brown, P; Jones, R J; Shultz, L D; Civin, C I

    2010-11-01

    In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tmlWjl)/SzJ (NOD-severe combined immune deficient (scid) IL2rg(-/-)) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg(-/-) mice. In this highly sensitive NOD-scid-IL2Rg(-/-)-based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.

  11. Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

    Science.gov (United States)

    Maude, Shannon L; Fitzgerald, Julie C; Fisher, Brian T; Li, Yimei; Huang, Yuan-Shung; Torp, Kari; Seif, Alix E; Kavcic, Marko; Walker, Dana M; Leckerman, Kateri H; Kilbaugh, Todd J; Rheingold, Susan R; Sung, Lillian; Zaoutis, Theoklis E; Berg, Robert A; Nadkarni, Vinay M; Thomas, Neal J; Aplenc, Richard

    2014-02-01

    Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. Forty-three children's hospitals contributing data to the Pediatric Health Information System database. Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. None. One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology

  12. Pseudo chediak-higashi granules in acute lymphoblastic leukemia: a rare entity.

    Science.gov (United States)

    Agrawal, Pallavi; Kumar, Narender; Sharma, Prashant; Varma, Subhash; Varma, Neelam

    2014-09-01

    Pseudo-Chediak-Highashi granules are giant cytoplasmic inclusions commonly encountered in myeloblasts or other myeloid precursors in acute myeloid leukemia and myelodysplastic syndromes. They derive their name from the inherited Chediak-Higashi syndrome that presents with oculocutaneous albinism, chronic infections and platelet dense granule deficiency. We report possibly the third case in world literature where these granules were seen in the blast cells of acute lymphoblastic leukemia in a 15-year-old male.

  13. Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

    2017-01-01

    Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransfe......Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

  14. Acute monocytic leukemia in a dog with X-linked severe combined immunodeficiency.

    OpenAIRE

    Felsburg, P J; Somberg, R L; Krakowka, G S

    1994-01-01

    We describe the occurrence of acute monocytic leukemia in a dog with X-linked severe combined immunodeficiency (XSCID) that had been raised in a gnotobiotic environment for 20 months. This case represents the first reported instance of malignancy in canine XSCID, the first case of acute monocytic leukemia in any species with severe combined immunodeficiency, and the first documented malignancy in any species with XSCID that was not associated with immunotherapy.

  15. Construction of protein profile classification model and screening of proteomic signature of acute leukemia

    OpenAIRE

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flig...

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

    International Nuclear Information System (INIS)

    Smith, D.; Bloch, S.; Al-Rashid, R.A.

    1980-01-01

    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.)

  17. Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers

    International Nuclear Information System (INIS)

    Porfiri, E.; Hoffbrand, A.V.; Wickremasinghe, R.G.

    1991-01-01

    Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. The authors have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with [3H] inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid-derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA-treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation

  18. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

    2016-08-19

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  19. Leukemia

    Science.gov (United States)

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

  20. Diagnostic value of CD117 in differential diagnosis of acute leukemias.

    Science.gov (United States)

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

    2014-07-01

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

  1. Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias.

    Science.gov (United States)

    Wang, K; Sanchez-Martin, M; Wang, X; Knapp, K M; Koche, R; Vu, L; Nahas, M K; He, J; Hadler, M; Stein, E M; Tallman, M S; Donahue, A L; Frampton, G M; Lipson, D; Roels, S; Stephens, P J; Sanford, E M; Brennan, T; Otto, G A; Yelensky, R; Miller, V A; Kharas, M G; Levine, R L; Ferrando, A; Armstrong, S A; Krivtsov, A V

    2017-01-01

    Genomic studies have identified recurrent somatic mutations in acute leukemias. However, current murine models do not sufficiently encompass the genomic complexity of human leukemias. To develop preclinical models, we transplanted 160 samples from patients with acute leukemia (acute myeloid leukemia, mixed lineage leukemia, B-cell acute lymphoblastic leukemia, T-cell ALL) into immunodeficient mice. Of these, 119 engrafted with expected immunophenotype. Targeted sequencing of 374 genes and 265 frequently rearranged RNAs detected recurrent and novel genetic lesions in 48 paired primary tumor (PT) and patient-derived xenotransplant (PDX) samples. Overall, the frequencies of 274 somatic variant alleles correlated between PT and PDX samples, although the data were highly variable for variant alleles present at 0-10%. Seventeen percent of variant alleles were detected in either PT or PDX samples only. Based on variant allele frequency changes, 24 PT-PDX pairs were classified as concordant while the other 24 pairs showed various degree of clonal discordance. There was no correlation of clonal concordance with clinical parameters of diseases. Significantly more bone marrow samples than peripheral blood samples engrafted discordantly. These data demonstrate the utility of developing PDX banks for modeling human leukemia, and emphasize the importance of genomic profiling of PDX and patient samples to ensure concordance before performing mechanistic or therapeutic studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Genomics of Acute Myeloid Leukemia Diagnosis and Pathways.

    Science.gov (United States)

    Bullinger, Lars; Döhner, Konstanze; Döhner, Hartmut

    2017-03-20

    In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such mutations may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. In contrast, mutations involving NPM1 or signaling molecules (eg, FLT3, RAS) typically are secondary events that occur later during leukemogenesis. Genetic data are now being used to inform disease classification, risk stratification, and clinical care of patients. Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current update of the WHO classification of myeloid neoplasms and AML, and mutations in three genes- RUNX1, ASXL1, and TP53-have been added in the risk stratification of the 2017 European LeukemiaNet recommendations for AML. Integrated evaluation of baseline genetics and assessment of minimal residual disease are expected to further improve risk stratification and selection of postremission therapy. Finally, the identification of disease alleles will guide the development and use of novel molecularly targeted therapies.

  4. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L-asparagina......BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...

  5. Context-selective death of acute myeloid leukemia cells triggered by the novel hybrid retinoid-HDAC inhibitor MC2392.

    Science.gov (United States)

    De Bellis, Floriana; Carafa, Vincenzo; Conte, Mariarosaria; Rotili, Dante; Petraglia, Francesca; Matarese, Filomena; Françoijs, Kees-Jan; Ablain, Julien; Valente, Sergio; Castellano, Rèmy; Goubard, Armelle; Collette, Yves; Mandoli, Amit; Martens, Joost H A; de Thé, Hugues; Nebbioso, Angela; Mai, Antonello; Stunnenberg, Hendrik G; Altucci, Lucia

    2014-04-15

    HDAC inhibitors (HDACi) are widely used in the clinic to sensitize tumorigenic cells for treatment with other anticancer compounds. The major drawback of HDACi is the broad inhibition of the plethora of HDAC-containing complexes. In acute promyelocytic leukemia (APL), repression by the PML-RARα oncofusion protein is mediated by an HDAC-containing complex that can be dissociated by pharmacologic doses of all trans retinoic acid (ATRA) inducing differentiation and cell death at the expense of side effects and recurrence. We hypothesized that the context-specific close physical proximity of a retinoid and HDACi-binding protein in the repressive PML-RARα-HDAC complex may permit selective targeting by a hybrid molecule of ATRA with a 2-aminoanilide tail of the HDAC inhibitor MS-275, yielding MC2392. We show that MC2392 elicits weak ATRA and essentially no HDACi activity in vitro or in vivo. Genome-wide epigenetic analyses revealed that in NB4 cells expressing PML-RARα, MC2392 induces changes in H3 acetylation at a small subset of PML-RARα-binding sites. RNA-seq reveals that MC2392 alters expression of a number of stress-responsive and apoptotic genes. Concordantly, MC2392 induced rapid and massive, caspase-8-dependent cell death accompanied by RIP1 induction and ROS production. Solid and leukemic tumors are not affected by MC2392, but expression of PML-RARα conveys efficient MC2392-induced cell death. Our data suggest a model in which MC2392 binds to the RARα moiety and selectively inhibits the HDACs resident in the repressive complex responsible for the transcriptional impairment in APLs. Our findings provide proof-of-principle of the concept of a context-dependent targeted therapy. ©2014 AACR.

  6. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kantarjian, Hagop M; DeAngelo, Daniel J; Stelljes, Matthias; Martinelli, Giovanni; Liedtke, Michaela; Stock, Wendy; Gökbuget, Nicola; O'Brien, Susan; Wang, Kongming; Wang, Tao; Paccagnella, M Luisa; Sleight, Barbara; Vandendries, Erik; Advani, Anjali S

    2016-08-25

    The prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy. In this phase 3 trial, we randomly assigned adults with relapsed or refractory acute lymphoblastic leukemia to receive either inotuzumab ozogamicin (inotuzumab ozogamicin group) or standard intensive chemotherapy (standard-therapy group). The primary end points were complete remission (including complete remission with incomplete hematologic recovery) and overall survival. Of the 326 patients who underwent randomization, the first 218 (109 in each group) were included in the primary intention-to-treat analysis of complete remission. The rate of complete remission was significantly higher in the inotuzumab ozogamicin group than in the standard-therapy group (80.7% [95% confidence interval {CI}, 72.1 to 87.7] vs. 29.4% [95% CI, 21.0 to 38.8], P<0.001). Among the patients who had complete remission, a higher percentage in the inotuzumab ozogamicin group had results below the threshold for minimal residual disease (0.01% marrow blasts) (78.4% vs. 28.1%, P<0.001); the duration of remission was longer in the inotuzumab ozogamicin group (median, 4.6 months [95% CI, 3.9 to 5.4] vs. 3.1 months [95% CI, 1.4 to 4.9]; hazard ratio, 0.55 [95% CI, 0.31 to 0.96]; P=0.03). In the survival analysis, which included all 326 patients, progression-free survival was significantly longer in the inotuzumab ozogamicin group (median, 5.0 months [95% CI, 3.7 to 5.6] vs. 1.8 months [95% CI, 1.5 to 2.2]; hazard ratio, 0.45 [97.5% CI, 0.34 to 0.61]; P<0.001); the median overall survival was 7.7 months (95% CI, 6.0 to 9.2) versus 6.7 months (95% CI, 4.9 to 8.3), and the hazard ratio was 0.77 (97.5% CI, 0.58 to 1.03) (P=0.04). In the safety population, the most frequent grade 3 or higher

  7. Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

    International Nuclear Information System (INIS)

    Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

    1978-01-01

    The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

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

    International Nuclear Information System (INIS)

    Sato, Junko; Abe, Takanori; Watanabe, Tsutomu

    1988-01-01

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

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

    Science.gov (United States)

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

    2014-05-28

    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 at the point of the first symptoms of leukemic disease, as happened with the case presented here. A 7-year-old Asian Balinese boy presented with back pain. His anteroposterior pelvic radiograph showed osteoporotic bone. A bone age study revealed growth failure of his metacarpals, phalanges and sesamoid. His total bone mass density was 97% age-match. However, a peripheral blood smear showed normochromic anemia with thrombocytopenia. Immunophenotyping of his peripheral blood revealed no dominant markers, but a bone marrow aspiration confirmed a diagnosis of acute lymphoblastic leukemia. Osteoporosis was the only manifestation of the child's underlying acute lymphoblastic leukemia. Leukemia was diagnosed when his bone marrow was found to contain more than 25% blasts. Because of leucopenia, the immunophenotype failed to reveal a dominant marker in this case, thus we were unable to classify the acute lymphoblastic leukemia.

  10. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mayur D. Mody MD

    2017-02-01

    Full Text Available Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  11. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Science.gov (United States)

    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  12. Diagnosis of a case of relapse of acute lymphoblastic leukemia based on oral manifestation of leukemic gingival enlargement and acute necrotizing gingivitis: A case report

    Directory of Open Access Journals (Sweden)

    Gopikrishna Kolli

    2014-01-01

    Full Text Available Acute leukemias are the most common malignancy in childhood. They represent approximately 30% of malignant diseases in patients under the age of 15 years. Acute lymphoblastic leukemia (ALL is the most frequent type of leukemia in children. Despite high cure rates, approximately 20% of patients with ALL have disease relapse. Oral manifestations are common in leukemia, particularly in acute leukemias. One of the oral manifestations of leukemia is diffuse gingival enlargement thought to be, at least partly, the result of gross infiltration of the gingiva by blast cells. The occurrence of acute necrotizing gingivitis, although a rare occurrence, is seen in such immunocompromised individuals. This is a case report of a 19-year-old patient who was under remission after treatment for ALL in whom a recurrence of leukemia was detected based on the oral findings and highlights the importance of its early detection by the dentist in preventing further complications and for instituting therapy swiftly.

  13. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  14. Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials.

    Science.gov (United States)

    Pollyea, Daniel A; Gutman, Jonathan A; Gore, Lia; Smith, Clayton A; Jordan, Craig T

    2014-08-01

    Despite an increasingly rich understanding of its pathogenesis, acute myeloid leukemia remains a disease with poor outcomes, overwhelmingly due to disease relapse. In recent years, work to characterize the leukemia stem cell population, the disease compartment most difficult to eliminate with conventional therapy and most responsible for relapse, has been undertaken. This, in conjunction with advances in drug development that have allowed for increasingly targeted therapies to be engineered, raises the hope that we are entering an era in which the leukemia stem cell population can be eliminated, resulting in therapeutic cures for acute myeloid leukemia patients. For these therapies to become available, they must be tested in the setting of clinical trials. A long-established clinical trials infrastructure has been employed to shepherd new therapies from proof-of-concept to approval. However, due to the unique features of leukemia stem cells, drugs that are designed to specifically eliminate this population may not be adequately tested when applied to this model. Therefore, in this review article, we seek to identify the relevant features of acute myeloid leukemia stem cells for clinical trialists, discuss potential strategies to target leukemia stem cells, and propose a set of guidelines outlining the necessary elements of clinical trials to allow for the successful testing of stem cell-directed therapies. Copyright© Ferrata Storti Foundation.

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

    International Nuclear Information System (INIS)

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    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 LOPAC 1280 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

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

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

    International Nuclear Information System (INIS)

    Kembhavi, Seema A.; Somvanshi, Snehal; Banavali, Shripad; Kurkure, Purna; Arora, Brijesh

    2012-01-01

    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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  19. Chromosomal abnormalities and environmental exposures in acute nonlymphocytic leukemia

    International Nuclear Information System (INIS)

    Crane, M.M.; Keating, M.J.; Trujillo, J.M.; Labarthe, D.R.

    1988-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Adi, Y. A., E-mail: yudi.adi@math.uad.ac.id [Department of Mathematic Faculty of MIPA Universitas Ahmad Dahlan (Indonesia); Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Kusumo, F. A.; Aryati, L. [Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Hardianti, M. S. [Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada (Indonesia)

    2016-04-06

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Poor survival of treatment-related acute nonlymphocytic leukemia

    International Nuclear Information System (INIS)

    Neugut, A.I.; Nieves, J.; Murray, T.; Tsai, Weiyann; Robinson, E.

    1990-01-01

    Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients

  3. Maxillo-orbital granulocytic sarcoma in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2016-01-01

    Full Text Available Granulocytic sarcoma or chloroma, a manifestation of acute myeloid leukemia (AML is a rare cause of childhood proptosis. A 14-year-old boy presented with progressively increasing unilateral proptosis and swelling of lower eyelid and face on the right side. Contrast enhanced computed tomographic images revealed enhancing infiltrates occupying the right orbit, maxillary antrum, and infratemporal fossa. Incisional biopsy from the orbital swelling and the bone marrow aspirate showing leukemic blast cells confirmed the diagnosis of AML. The peripheral smear was normal initially, but high total leukocytic count with immature blast cells was evident after 1-month of presentation. Chemotherapy brought about the remission of the disease. However, the delay in diagnosis because of negative peripheral blood smear examination and inconclusive fine-needle aspiration biopsy led to the loss of vision in right eye. Diagnosis of such case can be made by a combination of good clinical examination and relevant investigations. This case of maxillo-orbital granulocytic sarcoma is reported because of its rarity and to emphasize the clinical and cyto-histological features and problems concerning differential diagnosis.

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

    Science.gov (United States)

    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.

  5. Current diagnosis and treatment for pediatric acute myeloid leukemia.

    Science.gov (United States)

    Shiba, Norio

    2017-01-01

    Acute myeloid leukemia (AML) is a complex disease caused by chromosomal aberrations, mutations, epigenetic modifications, and the deregulated expression of genes, leading to increased myeloid cell proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains a challenge even after incorporating these molecular markers. Currently, some genetic mutations that allow risk stratification have been identified in adult AML, including DNMT3A and IDH1/2. However, these mutations are rare in pediatric AML cases, indicating that a different pathogenesis may exist between adult and pediatric AML. To reveal further details of pediatric AML pathogenesis, the authors performed whole-exome sequencing and whole-transcriptome analysis using massively parallel sequencing technologies in addition to gene expression array. We found that PRDM16 and EVI1-overexpressing patients had significantly worse overall survival and event-free survival, and these overexpressed genes were useful for stratifying patients with FLT3-ITD positive and/or normal karyotype. In order to further this work and establish more appropriate risk classification and molecular target drug development, target validation clinical studies are needed and expected.

  6. Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice.

    Science.gov (United States)

    Luskin, Marlise R; DeAngelo, Daniel J

    2017-08-01

    Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.

  7. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations.

    Science.gov (United States)

    Lindsley, R Coleman; Mar, Brenton G; Mazzola, Emanuele; Grauman, Peter V; Shareef, Sarah; Allen, Steven L; Pigneux, Arnaud; Wetzler, Meir; Stuart, Robert K; Erba, Harry P; Damon, Lloyd E; Powell, Bayard L; Lindeman, Neal; Steensma, David P; Wadleigh, Martha; DeAngelo, Daniel J; Neuberg, Donna; Stone, Richard M; Ebert, Benjamin L

    2015-02-26

    Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637. © 2015 by The American Society of Hematology.

  8. Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Figueroa, Maria E.; Chen, Shann-Ching; Andersson, Anna K.; Phillips, Letha A.; Li, Yushan; Sotzen, Jason; Kundu, Mondira; Downing, James R.; Melnick, Ari; Mullighan, Charles G.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy and is characterized by recurring structural genetic alterations. Previous studies of DNA methylation suggest epigenetic alterations may also be important, but an integrated genome-wide analysis of genetic and epigenetic alterations in ALL has not been performed. We analyzed 137 B-lineage and 30 T-lineage childhood ALL cases using microarray analysis of DNA copy number alterations and gene expression, and genome-wide cytosine methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) assay. We found that the different genetic subtypes of ALL are characterized by distinct DNA methylation signatures that exhibit significant correlation with gene expression profiles. We also identified an epigenetic signature common to all cases, with correlation to gene expression in 65% of these genes, suggesting that a core set of epigenetically deregulated genes is central to the initiation or maintenance of lymphoid transformation. Finally, we identified aberrant methylation in multiple genes also targeted by recurring DNA copy number alterations in ALL, suggesting that these genes are inactivated far more frequently than suggested by structural genomic analyses alone. Together, these results demonstrate subtype- and disease-specific alterations in cytosine methylation in ALL that influence transcriptional activity, and are likely to exert a key role in leukemogenesis. PMID:23921123

  9. FLT-3 ITD Positive Acute Basophilic Leukemia with Rare Complex Karyotype Presenting with Acute Respiratory Failure: Case Report

    Directory of Open Access Journals (Sweden)

    Antohe Ion

    2018-01-01

    Full Text Available Background: Acute basophilic leukemia is a rare subtype of acute myeloid leukemia, as categorized by the 2008 World Health Organization classification of myeloid neoplasms. Acute basophilic leukemia diagnosis requires thorough morphological, cytochemical, immunophenotypic, molecular, and cytogenetic studies and exclusion of other hematological neoplasms associating basophilia. The disease course is defined by histamine driven, occasionally life-threatening respiratory, cardiovascular, cutaneous or digestive complications, as well as primary refractoriness to standard therapy. Clinical presentation: We herein report a case of a 63-year-old asthmatic female patient diagnosed with acute basophilic leukemia, associated with previously unpublished cytogenetic features and FLT-3 ITD mutation, pulmonary leukostasis and spontaneous pulmonary capillary leak syndrome, which worsened immediately following chemotherapy initiation. Respiratory complications were successfully managed, but recrudesced upon emergence of refractory disease and were ultimately fatal. We highlight the likelihood of pulmonary complications induced by basophil degranulation and tumor lysis in hypercellular acute basophilic leukemia and the potential benefit of histamine receptor blockade in this setting.

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

    International Nuclear Information System (INIS)

    Laningham, Fred H.; Kun, Larry E.; Reddick, Wilburn E.; Ogg, Robert J.; Morris, E.B.; Pui, Ching-Hon

    2007-01-01

    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

  11. Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Juul, Anders; Lausten-Thomsen, Ulrik

    2011-01-01

    Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrenal...

  12. T-cell transcription factor GATA-3 is an immunophenotypic marker of acute leukemias with T-cell differentiation.

    Science.gov (United States)

    Dorfman, David M; Morgan, Elizabeth A; Pelton, Ashley; Unitt, Christine

    2017-07-01

    T-cell transcription factor GATA-3, known to play a role in early T-cell development and in the development of T-cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T-lymphoblastic leukemia/lymphoma (22/22 cases), early T-cell precursor lymphoblastic leukemia (11/11 cases), and mixed-phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B-lymphoblastic leukemia (0/16 cases). In contrast, T-bet, the other T-cell transcription factor that controls Th1/Th2 T-cell fate, is not expressed to any significant extent in immature thymocytes or in cases of T-lymphoblastic leukemia or acute myeloid leukemia/myeloid sarcoma, but is expressed in most cases (15/16) of B-lymphoblastic leukemia and in mixed-phenotype acute leukemia, B/myeloid. GATA-3-positive acute leukemias with T-cell differentiation were also found to express proto-oncogene C-MYC, in an average of 52% of neoplastic cells, which, along with GATA-3, may contribute to leukemogenesis, as suggested by transgenic mouse models. We conclude that GATA-3 is a sensitive and specific marker for the diagnosis of acute leukemias with T-cell differentiation and may be a useful addition to the panel of immunophenotypic markers for the diagnostic evaluation of acute leukemias. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Cytogenetic Profile and Gene Mutations of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Nawaf Alkhayat

    2017-07-01

    Full Text Available Background: Childhood acute lymphoblastic leukemia (ALL is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. Aims: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. Materials and methods: Patients —We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis —Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations —Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835 using polymerase chain reaction methods. Result: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22, t(12;21, and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7% and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22, MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group ( P  = .031.The event-free survival was also found to be worse ( P

  14. Malignant Phyllodes Tumor and Acute Megakaryoblastic Leukemia Sharing a Common Clonal Origin

    Directory of Open Access Journals (Sweden)

    Yngvar Fløisand

    2013-01-01

    Full Text Available There is a well-known association in male patients between mediastinal germ cell tumors (GCT and hematologic malignancies, with a propensity towards acute megakaryoblastic leukemia. These rare malignancies have been shown to share a common clonal origin, often deduced from the finding of isochromosome 12p, i(12p, in cells from both the solid tumor and the leukemia, and thus are now known to represent different manifestations of the same clonal process. We treated a young female patient with a malignant phyllodes tumor followed by an acute megakaryoblastic leukemia and found several of the same marker chromosomes by karyotype analysis of cells from both the tumor and the leukemia implying a common clonal origin of the two. To the best of our knowledge, this has not been demonstrated in phyllodes tumors before, but indicates that the same type of leukemization may occur of this tumor as has been described in mediastinal GCT.

  15. Unraveling Glucocorticoid Resistance In MLLrearranged Infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    Vag, Tibor; Krumbein, Ines; Reichenbach, Juergen R.; Lopatta, Eric; Stenzel, Martin; Kaiser, Werner A.; Mentzel, Hans-Joachim; Kentouche, Karim; Beck, James; Renz, Diane M.

    2011-01-01

    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.)

  18. Utility of peripheral blood immunophenotyping by flow cytometry in the diagnosis of pediatric acute leukemia.

    Science.gov (United States)

    Metrock, Laura K; Summers, Ryan J; Park, Sunita; Gillespie, Scott; Castellino, Sharon; Lew, Glen; Keller, Frank G

    2017-10-01

    Childhood acute leukemia is traditionally diagnosed from a bone marrow aspirate (BMA). New-onset acute leukemia patients do not always have visible circulating blasts in the peripheral blood (PB) at diagnosis. While the role of bone marrow flow cytometry for the diagnosis of acute leukemia is well established, the utility of PB flow cytometry (PBFC) is unknown. We performed a single-institution retrospective analysis to compare PBFC versus BMA in establishing or excluding a diagnosis of childhood acute leukemia. We retrospectively identified 485 PBFC samples with concurrent BMA from 2008 to 2013. Results of four-color flow cytometry for immunophenotypic characterization of leukemic versus nonclonal disease were characterized. Sensitivity and specificity were calculated among patients without a known diagnosis or prior therapy. Among 485 samples eligible for analysis, 120 had negative PBFC and BMA, 359 had positive PBFC and BMA, 3 had negative PBFC and positive BMA, and 3 had positive PBFC and negative BMA. There were small but significant differences in sensitivity (100 vs. 93.8%; P = 0.002) and positive predictive value (100 vs. 93.8%; P = 0.002) favoring BMA over PBFC among those demonstrating absence of circulating morphologic blasts. PBFC has high sensitivity and specificity for the diagnosis of childhood acute leukemia. The predictive value of PBFC remains high for patients without visible circulating blasts and may enhance the diagnostic process for determining the indications for marrow testing. © 2017 Wiley Periodicals, Inc.

  19. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia

    OpenAIRE

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H.K.; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter ...

  20. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Rosalyn P. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Kaste, Sue C. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Department of Radiology, University of Tennessee, College of Medicine, Memphis, Tennessee (United States)

    2004-05-01

    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.)

  1. Phosphoproteomic profiling analysis in pediatric acute leukemias and in solid tumors of the adult

    International Nuclear Information System (INIS)

    Basso, G.; Nitti, D.

    2009-01-01

    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

  2. Successful hematopoietic cell transplantation in a patient with X-linked agammaglobulinemia and acute myeloid leukemia.

    Science.gov (United States)

    Abu-Arja, Rolla F; Chernin, Leah R; Abusin, Ghada; Auletta, Jeffery; Cabral, Linda; Egler, Rachel; Ochs, Hans D; Torgerson, Troy R; Lopez-Guisa, Jesus; Hostoffer, Robert W; Tcheurekdjian, Haig; Cooke, Kenneth R

    2015-09-01

    X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia. © 2015 Wiley Periodicals, Inc.

  3. TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells

    OpenAIRE

    Riz, Irene; Hawley, Teresa S; Luu, Truong V; Lee, Norman H; Hawley, Robert G

    2010-01-01

    Abstract Background The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Results Global gene expre...

  4. Identification of TP53 as an Acute Lymphocytic Leukemia Susceptibility Gene Through Exome Sequencing

    Science.gov (United States)

    Powell, Bradford C.; Jiang, Lichun; Muzny, Donna M.; Treviño, Lisa R.; Dreyer, ZoAnn E.; Strong, Louise C.; Wheeler, David A.; Gibbs, Richard A.; Plon, Sharon E.

    2014-01-01

    Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes. PMID:23255406

  5. Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis

    DEFF Research Database (Denmark)

    Ranta, Susanna; Palomäki, Maarit; Levinsen, Mette

    2017-01-01

    BACKGROUND: Each year approximately 200 children and adolescents are diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries, and 3% of these have central nervous system (CNS) involvement confirmed by leukemic cells in the cerebrospinal fluid (CSF) or neurological symptoms....... We sought to determine the significance of neuraxis imaging in such patients. PROCEDURE: Magnetic resonance images of children aged 1-17.9 with CNS leukemia at diagnosis of ALL were centrally reviewed and clinical data were retrieved from the medical records and the Nordic leukemia registry. Patients...

  6. Detection of anti-Toxoplasma gondii antibodies in chronic myeloid leukemia and acute myeloid leukemia patients

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Gharavi

    2017-09-01

    Full Text Available Background and Aim: Infection of Toxoplasma gondii is a worldwide distribution. Toxoplasmosis in patients who are immunocompromised by virtue of underlying leukemia disease has received relatively little attention. This study was aimed to evaluate IgG and IgM antibodies of T. gondii and to minimize the role of T. gondii and opportunistic infection complication at the early stage of infection in leukemia patients. Materials and Methods: The purpose of this assay was to measure anti-T. gondii IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA technique in leukemia patients. Results: IgG antibodies against T. gondii were detected by ELISA in 96 (56.4% leukemia patients and 72 (42.4% control group. IgM antibodies were found in 10 patients (5.9% with leukemia and 3 (1.8% in the corresponding. Conclusion: Our finding indicated that leukemia patients under immunosuppressive condition should not be neglected. Toxoplasmosis in leukemia patients as a main risk factor is considered, meanwhile in some patients, due to possibility of the presence of secondary infection that leads to severe toxoplasmosis.

  7. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia

    NARCIS (Netherlands)

    von Lindern, M.; Breems, D.; van Baal, S.; Adriaansen, H.; Grosveld, G.

    1992-01-01

    The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3' part of the CAN gene on chromosome 9 and the 5' part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to be involved in a case of acute undifferentiated leukemia

  8. FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

    International Nuclear Information System (INIS)

    Pašaliç, Z; Greif, P A; Jurinoviç, V; Mulaw, M; Kakadia, P M; Tizazu, B; Fröhlich-Archangelo, L; Krause, A; Bohlander, S K

    2011-01-01

    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

  9. Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.

    Science.gov (United States)

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

    2006-07-01

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

  10. Segmentation and Classification of Bone Marrow Cells Images Using Contextual Information for Medical Diagnosis of Acute Leukemias

    OpenAIRE

    Reta, Carolina; Altamirano, Leopoldo; Gonzalez, Jesus A.; Diaz-Hernandez, Raquel; Peregrina, Hayde; Olmos, Ivan; Alonso, Jose E.; Lobato, Ruben

    2015-01-01

    Morphological identification of acute leukemia is a powerful tool used by hematologists to determine the family of such a disease. In some cases, experienced physicians are even able to determine the leukemia subtype of the sample. However, the identification process may have error rates up to 40% (when classifying acute leukemia subtypes) depending on the physician's experience and the sample quality. This problem raises the need to create automatic tools that provide hematologists with a se...

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

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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. Base excision repair deficiency in acute myeloid leukemia

    International Nuclear Information System (INIS)

    Scheer, N.M.

    2009-01-01

    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 (H 2 O 2 ). 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 H 2 O 2 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

  14. Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Kawamata, Norihiko; Ogawa, Seishi; Seeger, Karl; Kirschner-Schwabe, Renate; Huynh, Thien; Chen, John; Megrabian, Nairi; Harbott, Jochen; Zimmermann, Martin; Henze, Günter; Schrappe, Martin; Bartram, Claus R; Koeffler, H Phillip

    2009-06-01

    Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse. Only two cases at initial diagnosis had a normal appearing genome by SNP-chip. All 14 cases had genomic alterations at relapse; and 10 of these had additional genomic abnormalities not present at diagnosis. Deletion of either the INK4A/ARF gene (2 cases) or the NF2 gene (2 cases) at 22q12.2 was an acquired genomic change at relapse. Loss of heterozygosity with normal copy number [uniparental disomy (UPD)] was detected in 3 cases as an additional genomic change at relapse. Interestingly, several genomic alterations, especially deletions, detected at initial diagnosis, disappeared at relapse, suggesting the ALL cells at relapse were minor clones at initial diagnosis and emerged at relapse. For several cases, trisomy at initial diagnosis changed to either UPD (2 cases) or normal appearing genome (2 cases). Further, we found disruption of PTPRD gene occurring at intron 23 as an additional genomic abnormality in one case. In summary, additional genomic changes are very common events in ALL at relapse; whether these abnormalities are associated with resistance to treatment remains to clarified in further studies.

  15. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mullighan, Charles G.; Su, Xiaoping; Zhang, Jinghui; Radtke, Ina; Phillips, Letha A.A.; Miller, Christopher B.; Ma, Jing; Liu, Wei; Cheng, Cheng; Schulman, Brenda A.; Harvey, Richard C.; Chen, I-Ming; Clifford, Robert J.; Carroll, William L.; Reaman, Gregory; Bowman, W. Paul; Devidas, Meenakshi; Gerhard, Daniela S.; Yang, Wenjian; Relling, Mary V.; Shurtleff, Sheila A.; Campana, Dario; Borowitz, Michael J.; Pui, Ching-Hon; Smith, Malcolm; Hunger, Stephen P.; Willman, Cheryl L.; Downing, James R.

    2009-01-01

    Background Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. Methods We studied a cohort of 221 children with high-risk B-cell–progenitor ALL with the use of single-nucleotide–polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1–positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell–progenitor ALL. Results More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients in the original cohort); PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Using copy-number abnormalities, we identified a predictor of poor outcome that was validated in the independent validation cohort. This predictor was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS. The gene-expression signature of the group of patients with a poor outcome revealed increased expression of hematopoietic stem-cell genes and reduced expression of B-cell–lineage genes, and it was similar to the signature of BCR-ABL1–positive ALL, another high-risk subtype of ALL with a high frequency of IKZF1 deletion. Conclusions Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell–progenitor ALL. PMID:19129520

  16. Genomic Classification and Prognosis in Acute Myeloid Leukemia.

    Science.gov (United States)

    Papaemmanuil, Elli; Gerstung, Moritz; Bullinger, Lars; Gaidzik, Verena I; Paschka, Peter; Roberts, Nicola D; Potter, Nicola E; Heuser, Michael; Thol, Felicitas; Bolli, Niccolo; Gundem, Gunes; Van Loo, Peter; Martincorena, Inigo; Ganly, Peter; Mudie, Laura; McLaren, Stuart; O'Meara, Sarah; Raine, Keiran; Jones, David R; Teague, Jon W; Butler, Adam P; Greaves, Mel F; Ganser, Arnold; Döhner, Konstanze; Schlenk, Richard F; Döhner, Hartmut; Campbell, Peter J

    2016-06-09

    Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice. We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes. We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials. The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT

  17. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  18. Drug Repurposing for the Treatment of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Vibeke Andresen

    2017-11-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine. Novel therapy developments form a basis for novel multimodality therapy and include liposomal daunorubicin/cytarabine, broad or FLT3-specific tyrosine kinase inhibitors, Bcl-2 family inhibitors, selective inhibitors of nuclear export, metabolic inhibitors, and demethylating agents. The use of non-transplant immunotherapy is in early development in AML with the exceptional re-approval of a toxin-conjugated anti-CD33. However, the full potential of small molecule inhibitors and modalities like immunological checkpoint inhibitors, immunostimulatory small molecules, and CAR-T cell therapy is unknown. Some novel therapeutics will certainly benefit AML patient subgroups; however, due to high cost, more affordable alternatives are needed globally. Also the heterogeneity of AML will likely demand a broader repertoire of therapeutic molecules. Drug repurposing or repositioning represent a source for potential therapeutics with well-known toxicity profiles and reasonable prices. This implies that biomarkers of response need to accompany the development of antileukemic therapies for sharply defined patient subgroups. We will illustrate repurposing in AML with selected examples and discuss some experimental and regulatory limitations that may obstruct this development.

  19. Acute Myeloid Leukemia: analysis of epidemiological profile and survival rate.

    Science.gov (United States)

    de Lima, Mariana Cardoso; da Silva, Denise Bousfield; Freund, Ana Paula Ferreira; Dacoregio, Juliana Shmitz; Costa, Tatiana El Jaick Bonifácio; Costa, Imaruí; Faraco, Daniel; Silva, Maurício Laerte

    2016-01-01

    To describe the epidemiological profile and the survival rate of patients with acute myeloid leukemia (AML) in a state reference pediatric hospital. Clinical-epidemiological, observational, retrospective, descriptive study. The study included new cases of patients with AML, diagnosed between 2004 and 2012, younger than 15 years. Of the 51 patients studied, 84% were white; 45% were females and 55%, males. Regarding age, 8% were younger than 1 year, 47% were aged between 1 and 10 years, and 45% were older than 10 years. The main signs/symptoms were fever (41.1%), asthenia/lack of appetite (35.2%), and hemorrhagic manifestations (27.4%). The most affected extra-medullary site was the central nervous system (14%). In 47% of patients, the white blood cell (WBC) count was below 10,000/mm(3) at diagnosis. The minimal residual disease (MRD) was less than 0.1%, on the 15th day of treatment in 16% of the sample. Medullary relapse occurred in 14% of cases. When comparing the bone marrow MRD with the vital status, it was observed that 71.42% of the patients with type M3 AML were alive, as were 54.05% of those with non-M3 AML. The death rate was 43% and the main proximate cause was septic shock (63.6%). In this study, the majority of patients were male, white, and older than 1 year. Most patients with WBC count <10,000/mm(3) at diagnosis lived. Overall survival was higher in patients with MRD <0.1%. The prognosis was better in patients with AML-M3. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. Campylobacter jejuni Bacteremia in a Patient With Acute Lymphocytic Leukemia

    Science.gov (United States)

    Anvarinejad, Mojtaba; Amin Shahidi, Maneli; Pouladfar, Gholam Reza; Dehyadegari, Mohammad Ali; Mardaneh, Jalal

    2016-01-01

    Introduction Campylobacter jejuni is a slender, motile, non-spore-forming, helical-shaped, gram-negative bacterium. It is one of the most common causes of human gastroenteritis in the world. The aim of this study was to present a patient with acute lymphocytic leukemia (ALL), who was infected with Campylobacter jejuni. Case Presentation We describe the medical records of a pediatric ALL patient with bacteremia caused by C. jejuni, who was diagnosed at Amir hospital, Shiraz, Iran. This 14-year-old male visited the emergency department of Amir hospital with night sweats, severe polar high-grade fever, reduced appetite, and nausea in August 2013. Given the suspected presence of an anaerobic or microaerophilic microorganism, aerobic and anaerobic blood cultures were performed using an automated blood cultivator, the BACTEC 9240 system. In order to characterize the isolate, diagnostic biochemical tests were used. Antibiotic susceptibility testing was done with the disk diffusion method. The primary culture was found to be positive for Campylobacter, and the subculture of the solid plate yielded a confluent growth of colonies typical for Campylobacter, which was identified as C. jejuni by morphological and biochemical tests. The isolate was resistant to ciprofloxacin, cefotaxime, cephalexin, piperacillin/tazobactam, nalidixic acid, aztreonam, cefuroxime, cefixime, ceftazidime, and tobramycin. Conclusions C. jejuni should be considered in the differential diagnosis as a potential cause of bacteremia in immunosuppressed patients. In cases where the BACTEC result is positive in aerobic conditions but the organism cannot be isolated, an anaerobic culture medium is suggested, especially in immunocompromised patients. PMID:27621914

  1. Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells.

    Science.gov (United States)

    Lopes-Coelho, Filipa; Nunes, Carolina; Gouveia-Fernandes, Sofia; Rosas, Rita; Silva, Fernanda; Gameiro, Paula; Carvalho, Tânia; Gomes da Silva, Maria; Cabeçadas, José; Dias, Sérgio; Gonçalves, Luís G; Serpa, Jacinta

    2017-10-10

    Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment. Their metabolic adaptation relies on high rates of glycolysis to generate intermediates for PPP to support cell proliferation, and on the consumption of glycolysis-generated lactate to supply biomass and energy production. VEGF orchestrates this metabolic network by regulating MCT1 expression. Bromopyruvic acid (BPA) was proven to be an effective cytotoxic in AML, possibly transported by MCT1. Our study reinforces that targeting metabolism can be a good strategy to fight cancer. MCT1 expression at the time of diagnosis can assist on the identification of AML patients that will benefit from BPA therapy. Additionally, MCT1 can be used in targeted delivery of conventional cytotoxic drugs.

  2. Identification of the translocation t(15;17) in acute myeloid leukemia (AML) initially classified as FAB M1: case report and review of the literature.

    Science.gov (United States)

    Braham Jmili, N; Omri, H; Senana Sendi, H; Fekih, S; Hizem, S; Sriha, B; Khelif, A; Saad, A; Kortas, M

    2006-01-01

    We report a case of a patient aged about 53 years, who initially presented with hematological disorders (WBC: 44000/mm3, Hb: 11g/dl, Pit: 127000/mm3) without tumoral syndrome. The Wright-Giemsa stained bone marrow and peripheral blood smears showed a population of blast cells characterized by cells with high N/C and strongly basophilic cytoplasm without granules. The nuclei were predominantly round. Nuclear chromatin was fine and contained small nucleoli. Cytochemisty was positive for peroxidase activity. Immunophenotyping showed myeloid typical markers of granulocytic lineage (MP0+, CD13+, CD33+, CD117+, CD34-). The karyotype revealed the expression of t(15;17) chromosomal translocation. The diagnosis of acute myeloid leukaemia (AML) was then evoked initially. The cytological features corresponded closely to the M1 subtype as defined in the FAB classification. The patient was treated with induction therapy according to the 7/3 protocol. One month later, he was discharged from hospital on hematological and cytogenetic remission. He died at home because of a heart attack. From the biological findings the patient was retrospectively diagnosed as having promyelocytic leukemia (hyperbasophilic form).

  3. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

    Science.gov (United States)

    Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

    2015-09-01

    Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. 124

  4. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); H.B. Beverloo (Berna); A.R.M. von Bergh (Anne); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2005-01-01

    textabstractDrug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7,

  5. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Feychting, Maria; Klaeboe, Lars

    2007-01-01

    We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort...

  6. Method of automating of the separation of blasts and lymphocytes in the diagnosis of acute myeloid leukemia

    Science.gov (United States)

    Blindar, V. N.; Nikitaev, V. G.; Polyakov, E. V.; Matveeva, I. I.

    2017-01-01

    The work deals with the separation of the lymphocytes of healthy patients from blasts of patients with acute myeloblastic leukemia (different variants of the disease). In this study the evaluation of textural characteristics has been done for nuclei of blood cells for cells classification and for the determination of a variant of acute myeloblastic leukemia.

  7. Aurora kinases in childhood acute leukemia: the promise of aurora B as therapeutic target

    Science.gov (United States)

    Hartsink-Segers, S A; Zwaan, C M; Exalto, C; Luijendijk, M W J; Calvert, V S; Petricoin, E F; Evans, W E; Reinhardt, D; de Haas, V; Hedtjärn, M; Hansen, B R; Koch, T; Caron, H N; Pieters, R; Den Boer, M L

    2013-01-01

    We investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse phase protein array. Both kinases were overexpressed in ALL and AML patients (PE2A-PBX1-translocated ALL cases (PE2A-PBX1-positive cases, were sensitive as well. In adult AML early clinical trials, clear responses are observed with barasertib. Here we show that inhibition of aurora B, more than aurora A, has an antiproliferative and pro-apoptotic effect on acute leukemia cells, indicating that particularly targeting aurora B may offer a new strategy to treat pediatric ALL and AML. PMID:22940834

  8. Malignant pleural effusion in acute myeloid leukemia with hepatitis B virus infection.

    Science.gov (United States)

    Suharti, C; Santosa; Setiawan, Budi

    2015-04-01

    Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML). Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification).

  9. Immunotherapy in Acute Leukemias: Implications and Perspectives Using Wt1 Antigen.

    Science.gov (United States)

    Cebinelli, Guilherme Cesar Martelossi; DE Sousa Pereira, Nathália; Sena, Michelle Mota; DE Oliveira, Carlos Eduardo Coral; Fujita, Thiago Cezar; DA Rocha, Sérgio Paulo Dejato; DE Abreu Oliveira, Francisco José; Marinello, Poliana Camila; Watanabe, Maria Angelica Ehara

    2016-08-01

    The WT1 gene encodes a transcription factor involved in regulation of many cellular processes, including proliferation, differentiation, mRNA processing and apoptosis, besides acting as a transcription repressor of growth factors and their receptors' genes. This gene is expressed at high levels in several types of cancers, including acute leukemias. In this regard, many studies have identified WT1 protein as a tumor antigen, considered a target molecule for clinical application in human acute leukemias. Immunotherapy using WT1 antigen has been effective in stimulating immune responses against leukemic cells. Regarding adoptive immunotherapy, the use of dendritic cells (DCs) for the WT1-specific cytotoxic T cells generation proved to be efficient in the development and maintenance of immunologic cells. Therefore, these therapeutic methods, that provided enthusiasm for moving ahead, highlight several opportunities and challenges to be used in clinical practice for managing acute leukemias. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Acute leukemia in children: A review of the current Indian data

    Directory of Open Access Journals (Sweden)

    Ramandeep Singh Arora

    2016-01-01

    Full Text Available Acute leukemias are the most common diagnostic group of childhood cancer. This review summarizes the published literature on reported current outcomes of childhood acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML from India. Overall survival in ALL ranged from 45% to 81% (commonly >60% and event-free survival ranged from 41% to 70% (commonly >50%. Outcome data for AML was patchy with varying duration of follow-up, but it can be inferred that 50-80% of treated patients had experienced an event (toxic death, refractory disease or relapse. It is imperative that going forward focus should be on collaborative efforts, which promote treatment of patients on risk-stratified adapted protocols based on local infrastructure, improvement in supportive care and encourage prospective multi-center clinical trials.

  11. Prognosis and complications of acute childhood leukemia after prophylactic treatment of the central nervous

    International Nuclear Information System (INIS)

    Hosoki, Takuno; Harada, Koshi; Ikeda, Hiro; Miyata, Toshiaki; Kawai, Ryuji.

    1980-01-01

    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)

  12. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Marc Heincelman MD

    2016-09-01

    Full Text Available Acute lymphoblastic leukemia (ALL in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

  13. The Effect of Aromatherapy on Insomnia and Other Common Symptoms Among Patients With Acute Leukemia

    Science.gov (United States)

    Blackburn, Lisa; Achor, Sara; Allen, Betty; Bauchmire, Nicole; Dunnington, Danielle; Klisovic, Rebecca; Naber, Steven; Roblee, Kirsten; Samczak, Angela; Tomlinson-Pinkham, Kelly; Chipps, Esther

    2017-07-01

    To determine if the use of aromatherapy improves insomnia and other common symptoms in hospitalized patients with newly diagnosed acute leukemia. A randomized, crossover, washout trial. An inpatient acute leukemia unit at the Arthur G. James Cancer Hospital and Richard L. Solove Research Institute of the Wexner Medical Center at Ohio State University in Columbus. 50 patients who were newly diagnosed with acute leukemia and hospitalized to receive their initial four weeks of intensive induction chemotherapy. Patients were offered a choice of three scents to be used during the trial: lavender, peppermint, or chamomile. Each patient was randomized to receive either the chosen aromatherapy intervention or a placebo intervention during alternate weeks, with a washout period in between. Sleep quality and other common symptoms were measured. Aromatherapy, sleep, insomnia, pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and well-being. Most patients reported poor quality sleep at baseline, but aromatherapy had a statistically significant positive impact. Improvements were noted in tiredness, drowsiness, lack of appetite, depression, anxiety, and well-being because of aromatherapy. Aromatherapy is a viable intervention for improving insomnia and other symptoms commonly experienced by patients with acute leukemia. Oncology nurses can employ aromatherapy safely and inexpensively, and with minimal training, as an effective tool in decreasing many symptoms that plague patients with leukemia. Patients can exercise a greater sense of control over their treatment environments through the use of aromatherapy.

  14. Current status of diagnosis and prognosis of infant acute leukemia in China.

    Science.gov (United States)

    Huang, Li-Bin; Guan, Xiao-Qing; Zhang, Ying-Chuan; Zhang, Xiao-Li; Ke, Zhi-Yong; Luo, Xue-Qun

    2009-12-01

    Treatment and outcome of infant acute leukemia (IAL) in developed countries have been well documented. However, reports summarizing diagnosis and outcome of IAL in developing countries are limited. Five hundred ninety seven pediatric patients were diagnosed with acute leukemia in our hospital between January 1997 and June 2008, of which 19 were younger than 12 months. Data from our 19 cases and the Chinese literature were analyzed. Of the 19 cases, 14 had acute lymphoblastic leukemia (ALL) and 5 had acute myeloid leukemia (AML) based on FAB classification. Immunophenotyping and molecular genetic analysis were performed in only 6 cases. Only 16% (3/19) of the infants received treatment. Two infants with immunophenotypic AML who abandoned treatment achieved spontaneous remission without chemotherapy within 2 and 4 months respectively. Combining our data with those from Chinese literature, less than one third of the infants had immunophenotypic and genetic verification of leukemia and 29% (18/63) of them received treatment. Family financial difficulties and physicians' lack of confidence in treatment outcome in IAL contributed to a high treatment abandonment rate and poor outcome. Public health insurance as well as physician education on current IAL treatment strategies may decrease treatment abandonment in China.

  15. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

    Directory of Open Access Journals (Sweden)

    te Kronnie Geertruy

    2009-06-01

    Full Text Available Abstract Background The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL and myeloblastic leukemia (AML, with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes. Methods Using Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set + 78 (test set ALL and AML patients with (24+13 and without (116+65 MLL rearrangements have been investigated performing class comparison (SAM and class prediction (PAM analyses. Results We identified a MLL translocation-specific (379 probes signature and a phenotype-specific (622 probes signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements. Conclusion Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.

  16. Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations.

    Science.gov (United States)

    Andersson, Anna; Olofsson, Tor; Lindgren, David; Nilsson, Björn; Ritz, Cecilia; Edén, Patrik; Lassen, Carin; Råde, Johan; Fontes, Magnus; Mörse, Helena; Heldrup, Jesper; Behrendtz, Mikael; Mitelman, Felix; Höglund, Mattias; Johansson, Bertil; Fioretos, Thoas

    2005-12-27

    Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)/PBX1, IGH@/MYC, ETV6(TEL)/RUNX1(AML1), 11q23/MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies.

  17. Acute respiratory failure in 3 children with juvenile myelomonocytic leukemia

    DEFF Research Database (Denmark)

    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...

  18. Acute Respiratory Failure in 3 Children With Juvenile Myelomonocytic Leukemia

    DEFF Research Database (Denmark)

    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...

  19. Contribution of Flow Cytometry to Acute Leukemia Classification in Tunisia

    Directory of Open Access Journals (Sweden)

    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.

  20. [Significance of WHO classification for acute leukemia and myelodysplastic syndrome].

    Science.gov (United States)

    Sugiura, Aya; Takeshita, Akihiro

    2006-11-01

    The FAB classification, proposed in 1976, is basically a morphological classification of leukemia and is now used worldwide. However, according to chromosome and genetic research development, some important data have been revealed to influence the prognosis of leukemia. Recently, the World Health Organization (WHO), in conjunction with the Society for Hematopathology and the European Association of Hematopathology, published a new classification. The WHO classification incorporated the results of chromosome and genetic analyses of leukemia. Some leukemias and lymphomas revealed genetic abnormalities, establishing a new disease entity in the WHO classification, and several genetic abnormalities affect drug sensitivity and prognosis. As the WHO classification is going to be used worldwide, we should update our understanding of its contents.