Hematopoiesis News Volume 6.40 | Oct 13 2015

New IDH1 Mutant Inhibitors for Treatment of Acute Myeloid Leukemia
Treatment of isocitrate dehydrogenase 1 (IDH1) mutant primary acute myeloid leukemia cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. [Nat Chem Biol] Abstract

A PI3K p110β-Rac Signaling Loop Mediates Pten-Loss-Induced Perturbation of Hematopoiesis and Leukemogenesis
Scientists showed that when they delete phosphatase and tensin homolog (PTEN) in hematopoietic stem cells (HSCs) using the Mx1-Cre system, p110β ablation prevents myeloproliferative neoplasia, improves HSC function and suppresses leukemia initiation. [Nat Commun] Full Article

Replication Stress Caused by Low MCM Expression Limits Fetal Erythropoiesis and Hematopoietic Stem Cell Functionality
Investigators showed, using a mouse strain with hypomorphic expression of the origin licensing factor mini-chromosome maintenance (MCM)3 that limiting origin licensing in vivo affects the functionality of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. [Nat Commun] Full Article

Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia
Researchers report that hematopoietic cells differentiated from human induced pluripotent stem cells harboring Noonan syndrome/juvenile myelomonocytic leukemia (JMML)-causing PTPN11 mutations recapitulated JMML features. [Cell Rep] Full Article | Graphical Abstract | Press Release

Co-Administration of the MTORC1/TORC2 Inhibitor INK128 and the Bcl-2/Bcl-XL Antagonist ABT-737 Kills Human Myeloid Leukemia Cells through Mcl-1 Down-Regulation and AKT Inactivation
INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.g., FLT3, IDH2, NPM1, and Kras, while exerting minimal toxicity toward normal hematopoietic CD34⁺ cells. [Haematologica] Abstract

All-trans Retinoic Acid Arrests Cell Cycle in Leukemic Bone Marrow Stromal Cells by Increasing Intercellular Communication through Connexin 43-Mediated Gap Junction
Investigators evaluated the potential effects of all-trans retinoic acid (ATRA) on cell cycle, proliferation, and apoptosis of leukemic bone marrow stromal cells. Effects of ATRA on connexin 43 expression and gap junctional intercellular communication were also examined. [J Hematol Oncol] Full Article

CLINICAL RESEARCH

Influence of Differently Licensed KIR2DL1-Positive Natural Killer Cells in Transplant Recipients with Acute Leukemia: A Japanese National Registry Study
Researchers analyzed 3866 recipients in the Japan national registry who underwent their first allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia or acute lymphoblastic leukemia from HLA-A, -B and -DRB1 allele-genomatched unrelated donors. [Biol Blood Marrow Transplant] Abstract

Variable Eculizumab Clearance Requires Pharmacodynamic Monitoring to Optimize Therapy for Thrombotic Microangiopathy after Hematopoietic Stem Cell Transplantation
Investigators examined the pharmacokinetics and pharmacodynamics of eculizumab in children and young adult hematopoietic stem cell transplant recipients with thrombotic microangiopathy and activated complement to determine drug dosing requirements for future efficacy trials. [Biol Blood Marrow Transplant]
Abstract | Graphical Abstract

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Bio-Path Holdings Announces Successful Completion of Cohort 7 of Phase Ib Clinical Trial Evaluating Liposomal Grb-2 in Acute Myeloid Leukemia
Bio-Path Holdings, Inc. announced the successful completion of Cohort 7 of its Phase Ib clinical trial evaluating the toxicity of its lead compound, liposomal Grb-2, combined with low-dose cytarabine chemotherapy in patients with advanced acute myeloid leukemia. [Bio-Path Holdings, Inc.] Press Release

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NEW Postdoctoral Fellow – iPSC Models of Hematologic Disorders (Icahn School of Medicine at Mount Sinai)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Leukemia Stem Cell Biology (Lund University)

Postdoctoral Fellow – Leukemia, Stem Cells and Development (Josep Carreras Leukemia Research Institute)

Postdoctoral Positions – Cancer and Developmental Biology (North Carolina Central University)

Assistant Professor – Stem Cell Biology (University of South Carolina)

Postdoctoral Position – Hematology and Immunology (University of Liege)

Director of Research – Oncology and Hematology (CancerCare Manitoba)

Postdoctoral Fellow – HMGA Chromatin Remodeling Proteins in Cancer and Stem Cell Biology (Johns Hopkins University School of Medicine)

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