Hematopoiesis News Volume 4.12 | Apr 2 2013

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    Hematopoiesis News 4.12 April 2, 2013
    Hematopoiesis News
         In this issue: Publications | ReviewsIndustry News | Policy News | Events | Jobs
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    TOP STORY
    Apc Regulates the Function of Hematopoietic Stem Cells Largely through β-Catenin-Dependent Mechanisms
    By genetic approach, scientists demonstrated that inactivation of β-catenin rescued the exhaustion of Apc-deficient hematopoietic stem/progenitor cells, thereby preventing bone marrow failure in Apc-deficient mice. [Blood] Abstract

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    PUBLICATIONS (Ranked by impact factor of the journal)

    LABORATORY RESEARCH

    Autoantigen Can Promote Progression to a More Aggressive TCL1 Leukemia by Selecting Variants with Enhanced B-Cell Receptor Signaling
    (Auto)antigen engagement by the B-cell receptor and possibly the sites where this occurs influence the outcome of chronic lymphocytic leukemia. To test if selection for autoreactivity leads to increased aggressiveness and if this selection plays out equally in primary and secondary tissues, researchers used T-cell leukemia (TCL)1 cells reactive with the autoantigen phosphatidylcholine. [Proc Natl Acad Sci USA] Abstract | Full Article

    Transposon Mutagenesis Reveals Cooperation of E-Twenty-Six Family Transcription Factors with Signaling Pathways in Erythro-Megakaryocytic Leukemia
    To define genetic lesions driving leukemia, the authors targeted cre-dependent Sleeping Beauty transposon mutagenesis to the blood-forming system using a hematopoietic-selective vav 1 oncogene promoter. [Proc Natl Acad Sci USA] Abstract

    mTOR Regulates DNA Damage Response through NF-κB-Mediated FANCD2 Pathway in Hematopoietic Cells
    Researchers showed that gene targeting of mammalian target of rapamycin (mTOR) in hematopoietic stem/progenitor cells causes a defective DNA damage response (DDR) to a variety of DNA damage agents, mimicking that caused by deficient FANCD2, a key component of the Fanconi anemia (FA) DDR machinery. [Leukemia] Abstract

    Global H3K4me3 Genome Mapping Reveals Alterations of Innate Immunity Signaling and Overexpression of JMJD3 in Human Myelodysplastic Syndrome CD34+ Cells
    Data indicate the deregulation of trimethylated histone 4 lysine 3 (H3K4me3) and associated abnormal activation of innate immunity signals play a role in the pathogenesis of myelodysplastic syndromes (MDS) and that targeting these signals may have potential therapeutic value in MDS. [Leukemia] Abstract

    Inosine Triphosphate Pyrophosphohydrolase (ITPA) Polymorphic Sequence Variants in Adult Hematological Malignancy Patients and Possible Association with Mitochondrial DNA Defects
    Investigators hypothesized that reduced ITPA activity may cause acquired mitochondrial DNA (mtDNA) defects. Furthermore, they investigated whether accumulating mtDNA defects may then be a risk factor for cell transformation, in adult hematological malignancy. [J Hematol Oncol] Abstract | Full Article

    The Src Homology 2 Protein Shb Promotes Cell Cycle Progression in Murine Hematopoietic Stem Cells by Regulation of Focal Adhesion Kinase Activity
    The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb’s known interaction partners are established regulators of blood cell development and function. Researchers explored hematopoietic stem and progenitor cell function in the Shb knockout mouse. [Exp Cell Res] Abstract

    Electrospun Nanofibers as a Bioadhesive Platform for Capturing Adherent Leukemia Cells
    Researchers investigated the adhesive behaviors of normal and abnormal hematopoietic cells on nanotopographical materials. Previously, electrospun nanofiber scaffolds (NFS) were used to capture and expand hematopoietic stem cells in vitro; here they demonstrated that NFS could also serve as a useful bioadhesive platform for capturing functionally adherent leukemia cells. [J Biomed Mater Res A] Abstract

    CLINICAL RESEARCH

    MRD-Directed Risk-Stratification Treatment May Improve Outcome of t (8;21) AML in the First Complete Remission: Results from AML05 Multicenter Trial
    Researchers aimed to improve outcome of t (8;21) acute myeloid leukemia (AML) in first complete remission by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. [Blood] Abstract

    A Variant in IRF3 Impacts on the Clinical Outcome of AML Patients Submitted to Allo-SCT
    Scientists analyzed two gene variants in IFN regulatory factor-3 (IRF3) (rs7251 and rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical sibling allo-SCT. [Bone Marrow Transplant] Abstract

    Etoposide in Combination with Low-Dose CAG (Cytarabine, Aclarubicin, G-CSF) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia: A Multicenter, Randomized Control Trial in Southwest China
    In a well-controlled multi-center randomized trial in southwestern China, 228 patients with refractory or relapsed acute myeloid leukemia received a low-dose CAG regimen either with etoposide or without etoposide. The complete remission rate, overall survival and toxicity were evaluated. [Leuk Res] Abstract

    Free Wallchart: Identification of Colonies Derived from Mouse Hematopoietic Progenitors

    REVIEWS
    Advances in Stem Cell Therapy against Gliomas
    Stem cell-based therapy using neural, mesenchymal, or hematopoietic stem cells may be an alternative approach because it is tumor selective and allows targeted therapy that spares healthy brain tissue. The authors discuss current trends and the latest developments in stem cell therapy against malignant gliomas from both the experimental laboratory and the clinic. [Trends Mol Med] Abstract

    Visit our reviews page to see a complete list of reviews in the hematopoietic research field.

    INDUSTRY NEWS

    Acceleron Receives Two FDA Orphan Designations for ACE-536
    Acceleron Pharma, Inc. announced that the United States Food and Drug Administration (FDA) granted orphan designation for ACE-536 for the treatment of beta-thalassemia and for the treatment of myelodysplastic syndromes, two rare blood disorders characterized by severe and chronic anemia. [Acceleron Pharma, Inc.] Press Release

    Pfizer’s BOSULIF® (bosutinib) Receives Conditional Marketing Authorization from the European Commission
    Pfizer Inc. announced that the European Commission has granted conditional marketing authorization for BOSULIF® in the European Union for the treatment of adult patients with chronic phase, accelerated phase and blast phase Philadelphia chromosome positive chronic myelogenous leukemia previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options. [Pfizer Inc.] Press Release

    Promising Stem Cell Therapy for Leukemia Patients
    Leukemia patients receive a bone marrow transplant, which allows them to build a “new” immune system. However, this immune system not only attacks cancer cells but healthy tissue too. Special antibodies will be used to protect healthy tissue in future. [Fraunhofer-Gesellschaft] Press Release

    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

    NEW 2013 In Vitro Biology Meeting
    June 15-19, 2013
    Providence, United States

    Visit our events page to see a complete list of events in the hematopoietic community.

    JOB OPPORTUNITIES

    Postdoctoral Position – Stem Cell Research (University of Washington)

    Lecturer or Reader – Associate Professor (University of Reading)

    Research Assistant – Stem Cell & Leukemia Epigenetics (King’s College London)

    Postdoctoral Position – Bioinformatics and Stem Cell Biology (University of Texas at Houston)

    Postdoctoral Position – Stem Cells and Cancer (Tsinghua University)

    Cord Blood Laboratory Manager (Puget Sound Blood Center)

    Postdoctoral Positions (Cancer Science Institute of Singapore)

    Postdoctoral Positions – Cell Death Signaling & Cancer (Goethe Universität Frankfurt, Institute for Experimental Cancer Research in Pediatrics)

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