Volume 6.40 | Oct 13

Hematopoiesis News 6.40 October 13, 2015
Hematopoiesis News
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Double Enzyme Hit May Explain Common Cancer Drug Side Effect
Some anti-leukemia treatments work by inhibiting Shp2 or other enzymes involved in the same cellular systems, but researchers have found that mice lacking both Pten and Shp2 can’t produce and sustain enough red blood cells. The study helps explain why anemia is a common side effect of anti-cancer drugs that target enzymes involved in tumor growth. [Press release from the University of California, San Diego discussing online publication in Proceedings of the National Academy of Sciences] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
PAR1 Signaling Regulates the Retention and Recruitment of EPCR-Expressing Bone Marrow Hematopoietic Stem Cells
Scientists report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR+) long-term repopulating hematopoietic stem cells in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). [Nat Med] Abstract

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


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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Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis and Chronic Myelomonocytic Leukemia
The authors outline the indications and modalities of hematopoietic stem cell transplantation as they pertain to the Philadelphia chromosome negative myeloproliferative neoplasms and CMML based on the currently available evidence. [Am J Hematol] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
SELLAS Life Sciences Reports Promising Top-Line Phase II Data for WT1 Vaccine in Mesothelioma and Acute Myeloid Leukemia Patients
SELLAS Life Sciences Group announced top-line data from the company’s Phase II clinical study of its WT1 cancer vaccine in patients with malignant pleural mesothelioma. [Press release from SELLAS Life Sciences Group (PR Newswire Association, LLC) discussing research to be presented at the 8th International WT1 Conference, Kyoto] Press Release

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Seattle Genetics Announces Initiation of Phase I/II Clinical Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with Opdivo® (Nivolumab) in Second-Line Hodgkin Lymphoma
Seattle Genetics, Inc. announced that it has initiated a Phase I/II clinical trial of ADCETRIS in combination with Opdivo for patients with relapsed or refractory Hodgkin lymphoma after failure of frontline treatment. [Seattle Genetics, Inc.] Press Release

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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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 28th Lorne Cancer Conference
February 11-13, 2016
Lorne, Australia

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Research Technician – Stem Cell and Gene Therapy (Fred Hutchinson Cancer Research Center)

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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