Volume 7.08 | Mar 1

Hematopoiesis News 7.08 March 1, 2016
Hematopoiesis News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
MSI2 Is Required for Maintaining Activated Myelodysplastic Syndrome Stem Cells
Scientists demonstrated that elevated MSI2 expression correlates with poor survival in myelodysplastic syndromes (MDS). Conditional deletion of Msi2 in a mouse model of MDS resulted in a rapid loss of MDS hematopoietic stem and progenitor cells and reverses the clinical features of MDS. [Nat Commun] Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Telomerase Gene Therapy Rescues Telomere Length, Bone Marrow Aplasia and Survival in Mice with Aplastic Anemia
Investigators tested the therapeutic efficacy of telomerase activation by using AAV9 gene therapy vectors carrying the telomerase Tert gene in two independent mouse models of aplastic anemia owing to short telomeres. They found that a high dose of AAV9-Tert targets the bone marrow compartment including hematopoietic stem cells. [Blood] Abstract

Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation
Scientists generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. [Dev Cell] Full Article | Graphical Abstract | Press Release

MEF2C and EBF1 Co-Regulate B Cell-Specific Transcription
Researchers identified early B cell factor-1 (EBF1) as a co-regulator of gene expression with myocyte enhancer factor 2C (MEF2C). A genome-wide survey of MEF2C and EBF1 binding sites identified a subset of B cell-specific genes that they target. [PLoS Genet] Full Article

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Contributes to the Proliferation of Hematopoietic Progenitor Cells in Murine Bone Marrow via PACAP-Specific Receptor
The authors assessed the expression of a PACAP-specific receptor (PAC1) gene and protein in mouse bone marrow. Cells strongly expressing PAC1+ were large in size, had oval nuclei, and merged with CD34+ cells, suggesting that the former were hematopoietic progenitor cells. Compared with wild-type mice, adcyap1−/− mice exhibited lower multiple potential progenitor cell populations and cell frequency in the S-phase of the cell cycle. [Sci Rep] Full Article

Hyper-Active Non-Homologous End Joining Selects for Synthetic Lethality Resistant and Pathological Fanconi Anemia Hematopoietic Stem and Progenitor Cells
Investigators showed that poly[ADP-ribose] polymerase 1 activation in hematopoietic stem and progenitor cells (HSPCs) in response to genotoxic or oxidative stress attenuates HSPC exhaustion. [Sci Rep] Full Article

BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo
Researchers found that the aorta-gonad-mesonephros (AGM) harbors two types of adult-repopulating hematopoietic stem cells (HSC) upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. [Stem Cell Reports] Full Article | Graphical Abstract

H2S Protects against Fatal Myelosuppression by Promoting the Generation of Megakaryocytes/Platelets
H2S promoted the generation of megakaryocytes, increased platelet levels, ameliorate entorrhagia, and improved survival. These H2S effects were blocked in both in vivo and in vitro models with thrombopoietin receptor knockout mice. [J Hematol Oncol] Full Article

CLINICAL RESEARCH

Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia
Researchers analyzed the outcome of 95 carefully characterized allogeneic hematopoietic stem cell transplant patients with mixed phenotype acute leukemia reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. [Biol Blood Marrow Transplant] Abstract

Alemtuzumab-BEAM as Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma: A Single-Center Analysis
The authors retrospectively analyzed the outcome of 20 patients with relapsed/refractory Hodgkin’s lymphoma who received allogeneic hematopoietic stem cell transplantation following conditioning therapy with alemtuzumab-BEAM. [J Cancer Res Clin Oncol] Abstract

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REVIEWS
Regain Control of p53: Targeting Leukemia Stem Cells by Isoform-Specific HDAC Inhibition
The authors summarize the current understanding of various mechanisms underlying deregulation of histone deacetylases (HDACs), which could be exploited to restore p53 activity and enhance targeting of leukemia stem cells in molecularly defined patient subsets. [Exp Hematol] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
 
INDUSTRY NEWS
CAR Trials Drive Leukemia and Lymphoma Treatment in New Direction
Researchers at Moores Cancer Center have launched three clinical trials to test the safety and efficacy of a novel cellular-immunotherapy that uses modified T cells – one of the immune system’s primary weapons – to treat three different types of blood cancer that often defy existing therapies. [UC San Diego Health] Press Release

National Institutes of Health’s NIAID Initiating Dose Evaluation Studies in Animal Models of Pluristem’s PLX-R18 in the Treatment of Acute Radiation Syndrome
Pluristem Therapeutics Inc. announced that the National Institute of Allergy and Infectious Diseases (NIAID) will initiate studies in large animals to evaluate dosing for Pluristem’s PLX-R18 as a medical counter measure in the treatment of the hematologic components of acute radiation syndrome. [Pluristem Therapeutics Inc.] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
Visit our events page to see a complete list of events in the hematopoiesis community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Hematology/Oncology (Boston Children’s Hospital)

NEW Postdoctoral Fellow – Cancer Stem Cell Biology (McGill University Health Center)

NEW Postdoctoral Fellow – Cancer Biology (National University of Singapore)

Lead Scientist – Translational Therapy (NHS Blood and Transplant)

PhD Position – Leukemogenesis and Treatment Resistance (Institute for Tumor Biology and Experimental Therapy)

Translational Research Scientist – Hematology/Oncology (University of Chicago)

Postdoctoral Associate – Epigenetic Regulation of Normal and Leukemic Stem Cells (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Researcher – Pre-Leukemic Stem Cells in the Thymus (Ghent University)

Laboratory Technician – Molecular Biology (Icahn School of Medicine at Mount Sinai)

Assistant/Associate/Full Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)


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