Acute Leukemias of Ambiguous Origin

Porwit, Anna; Béné, Marie C.

doi:10.1309/ajcpstu55drqegte

Cited by 47 publications

(40 citation statements)

References 38 publications

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“…The World Health Organization (WHO) has described the criteria for MPAL (1), though the clinical significance of risk classification of MPAL is not clear and treatment approaches have not been uniform across centers (2). The World Health Organization (WHO) has described the criteria for MPAL (1), though the clinical significance of risk classification of MPAL is not clear and treatment approaches have not been uniform across centers (2).…”

Section: Introductionmentioning

confidence: 99%

Flow cytometric false myeloperoxidase‐positive childhood B‐lineage acute lymphoblastic leukemia

Savaşan

Buck

Gadgeel

et al. 2018

Cytometry Part B Clinical

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Section: Introductionmentioning

confidence: 99%

Flow cytometric false myeloperoxidase‐positive childhood B‐lineage acute lymphoblastic leukemia

Savaşan

Buck

Gadgeel

et al. 2018

Cytometry Part B Clinical

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“…1,2 In contrast to acute lymphoblastic leukemia (ALL), treatment of AML has not improved substantially over the last two decades and many patients still fail to respond to standard intensive chemotherapy based on nucleoside analogs such as cytarabine (AraC) or fludarabine and anthracyclines such as idarubicin and daunorubicin. 3,4 Failure of current therapies to eradicate leukemia-initiating/propagating cells (LICs) and chemotherapy refractoriness are the major mechanisms underlying AML progression/relapse.…”

Section: Introductionmentioning

confidence: 99%

IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

et al. 2018

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Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients remain refractory or relapse upon standard chemotherapy based on nucleoside analogs plus anthracyclines. The crosstalk between AML cells and the BM stroma is a major mechanism underlying therapy resistance in AML. Lenalidomide and pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess pleiotropic anti-leukemic properties including potent immune-modulating effects and are commonly used in hematological malignances associated with intrinsic dysfunctional BM such as myelodysplastic syndromes and multiple myeloma. Whether IMiDs may improve the efficacy of current standard treatment in AML remains understudied. Here, we have exploited in vitro and in vivo preclinical AML models to analyze whether IMiDs potentiate the efficacy of AraC/Idarubicin-based standard AML chemotherapy by interfering with the BM stroma-mediated chemoresistance. We report that IMiDs do not exert cytotoxic effects on either non-del5q/5q- AML cells nor BM-MSCs, but they enhance the immunomodulatory properties of BM-MSCs. When combined with AraC/Idarubicin, IMiDs fail to circumvent BM stroma-mediated resistance of non-del5q/5q- AML cells in vitro and in vivo but induce robust extramedullary mobilization of AML cells. When administered as a single agent, lenalidomide specifically mobilizes non-del5q/5q- AML cells, but not healthy CD34+ cells, to peripheral blood (PB) through specific downregulation of CXCR4 in AML blasts. Global gene expression profiling supports a migratory/mobilization gene signature in lenalidomide-treated non-del5q/5q- AML blasts but not in CD34+ cells. Collectively, IMiDs mobilize non-del5q/5q- AML blasts to PB through CXCR4 downregulation, but fail to potentiate AraC/Idarubicin activity in preclinical models of non-del5q/5q- AML.

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“…These neoplasms are thought to arise from an immature undifferentiated progenitor that expresses both myeloid and lymphoid antigens. The lack of distinguishing morphologic or genomic features means diagnosis is based solely on blast immunophenotype 2 . Little is known about the biology of MPAL and as a result there is single standard induction chemotherapy approach with ALL and AML-type regimens used interchangeably.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia

Getta

Roshal

Zheng

et al. 2017

Biology of Blood and Marrow Transplantation

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Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pre-transplant therapy and transplant outcomes for 36 well characterized pediatric and adult patients with MPAL defined according to the 2016 WHO leukemia update. A predominance of ALL-associated mutations and cytogenetic abnormalities was noted. Remission rates after induction appeared comparable among adults (20/23) and children (11/13) and among those who received ALL (10/11) or AML-type (21/25) induction. Adults were transplanted in first remission while children were transplanted in the setting of relapse or MLL rearrangement. The median follow-up among the 25 patients who underwent transplantation was 39.6 months and median OS was not reached. Relapse after transplant was associated with MLL rearrangement (p=0.022), reduced intensity (p<0.001), and higher WBC at diagnosis (p=0.034). These data highlight differing therapeutic approaches between adult and pediatric MPAL and demonstrate favorable survival of adult MPAL patients consolidated with allogeneic hematopoietic cell transplantation.

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Acute Leukemias of Ambiguous Origin

Abstract: There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough.

Cited by 47 publications

References 38 publications

Flow cytometric false myeloperoxidase‐positive childhood B‐lineage acute lymphoblastic leukemia

Flow cytometric false myeloperoxidase‐positive childhood B‐lineage acute lymphoblastic leukemia

IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia

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