Hematopoiesis News Volume 4.35 | Sep 10 2013

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    Hematopoiesis News 4.35 September 10, 2013

    Hematopoiesis News

    In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs

    TOP STORY
    Identification of Gene Expression-Based Prognostic Markers in the Hematopoietic Stem Cells of Patients with Myelodysplastic Syndromes
    Several criteria that form the basis of the classifications and scoring systems most commonly used to diagnose myelodysplastic syndromes (MDS) in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, scientists have used gene expression profiling data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis. [J Clin Oncol] Abstract
    Take the 'if' out of 'diff': Reduce variability when differentiating to hematopoietic cells

    PUBLICATIONS (Ranked by impact factor of the journal)
    LABORATORY RESEARCH

    SP/Drug Efflux Functionality of Hematopoietic Progenitors Is Controlled by Mesenchymal Niche through VLA-4/CD44 Axis
    Scientists showed that Side Population (SP) functionality can be induced in lin cells from un-mobilized peripheral blood after nesting on mesenchymal stromal cells (MSC). This MSC-induced SP fraction contains hematopoietic stem/progenitor cells as demonstrated by their CD34+ cell percentage, quiescent status, in vitro proliferative and clonogenic potential, engraftment in NSG mice and stemness gene expression profile. [Leukemia] Abstract

    CBFB-MYH11/RUNX1 Together with a Compendium of Hematopoietic Regulators, Chromatin Modifiers and Basal Transcription Factors Occupies Self-Renewal Genes in inv(16) Acute Myeloid Leukemia
    Transcriptional analysis revealed that upon fusion protein knock down a small subset of CBFβ-MYH11 target genes show increased expression, confirming a role in transcriptional repression. However, the majority of CBFβ-MYH11 target genes, including genes implicated in hematopoietic stem cell self-renewal such as ID1, LMO1 and JAG1, are actively transcribed and repressed upon fusion protein knock down. [Leukemia] Abstract

    The Control of Hematopoietic Stem Cell Maintenance, Self-Renewal and Differentiation by Mysm1-Mediated Epigenetic Regulation
    Mysm1 is a recently identified histone H2A deubiquitinase with essential and intrinsic roles for maintaining functional hematopoietic stem cells (HSC). In this study, in addition to confirming this function of Mysm1, researchers provide more evidence for how Mysm1 controls HSC homeostasis using Mysm1-deficient mice. [Blood] Abstract

    Symplekin, a Polyadenylation Factor, Prevents MOZ and MLL Activity on HOXA9 in Hematopoietic Cells
    The authors have previously shown that monocytic leukemia zinc finger (MOZ) and mixed lineage leukemia (MLL) cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, they identified new proteins interacting with MOZ. [Biochim Biophys Acta] Abstract

    Cell Surface Notch1 Expression Identifies a Primitive Phenotype within CD34+CD38- Hematopoietic Cells
    Investigators examined the expression of human cell surface Notch1 in cord blood CD34+ cells and the function of Notch in CD34+ cells in vitro. [Eur J Haematol] Abstract

    Microfluidic Generation of Gradient Hydrogels to Modulate Hematopoietic Stem Cell Culture Environment
    While multiple biomolecular signals and bone marrow cell populations have been proposed as key regulators of hematopoietic stem cell (HSC) fate, new tools are required to probe their importance and mechanisms of action. A novel method based on a microfluidic mixing platform to create small volume, 3D hydrogel constructs containing overlapping patterns of cell and matrix constituents inspired by the HSC niche, is described. [Adv Healthc Mater] Abstract

    CLINICAL RESEARCH

    Hematopoietic Stem Cell Mobilization for Gene Therapy: Superior Mobilization by the Combination of Plerixafor plus GCSF in Patients with Thalassemia Major
    Successful stem cell gene therapy requires high numbers of genetically-engineered hematopoietic stem cells collected using optimal mobilization strategies. Researchers focused on stem cell mobilization strategies for thalassemia and present the results of a plerixafor-based mobilization trial with emphasis on the remobilization with G-CSF+plerixafor in those patients who have previously failed mobilization. [Hum Gene Ther] Abstract

    Pharmacokinetically-Targeted BU and Fludarabine as Conditioning before Allogeneic Hematopoietic Cell Transplantation for Adults with ALL in First Remission
    Researchers report a retrospective review of 65 patients with ALL in first remission receiving grafts from allogeneic donors after fludarabine 40 mg/m2/day for 4 days and i.v. BU targeted to a median daily area under the concentration-time curve below 6000 μmolesmin/L. [Bone Marrow Transpl] Abstract

    Incidence, Risk Factors, and Outcome of Bacteremia following Autologous Hematopoietic Stem Cell Transplantation in 720 Adult Patients
    Researchers analyzed the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after autologous hematopoietic stem cell transplantation. [Ann Hematol] Abstract

    Learn more about the new smartphone app for human blood cell frequencies

    REVIEWS
    Therapy Targets in Glioblastoma and Cancer Stem Cells: Lessons from Hematopoietic Neoplasms
    This review focuses on putative novel therapy targets represented by markers described to define cancer stem/initiating cells in malignant gliomas, which have been called ‘leukemia of the brain’, given their rapid migration and evolution. Parallels are drawn with other cancers, especially hematopoietic, given the similar rampant proliferation and treatment resistance of glioblastoma multiforme and secondary acute leukemias. [J Cell Mol Med] Full Article

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

    Stem Cell Society Singapore 2013 Symposium

    INDUSTRY NEWS
    America Stem Cell, Inc. Receives FDA Clearance for Its Multi-Center Nationwide Trial
    America Stem Cell, Inc. (ASC) announced it has received clearance from FDA for its Phase I/IIa nationwide multi-center dual-umbilical cord transplantation study evaluating ASC-101 in patients with hematologic malignancies and myelodysplastic syndrome. [MarketWatch, Inc.] Press Release

    Gamida Cell Announces the Successful Transplantation of the First Patient in the Company’s Phase I/II Study of NiCord® in a Single Cord Configuration
    Gamida Cell announced that the first patient has been successfully transplanted in the company’s second Phase I/II study of NiCord®, as an alternative, experimental treatment for blood cancers. The transplant took place at Duke University Medical Center. [Gamida Cell] 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)

    From our sponsor: Free mouse hematopoietic progenitors wallchart. Request your copy.

    EVENTS
    NEW 2013 American Society of Hematology (ASH) Annual Meeting and Exposition
    December 7-10, 2013
    New Orleans, United States

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

    JOB OPPORTUNITIES
    NEW Postdoctoral Fellow – Mechanisms that Regulate Stem Cell Self-Renewal Using Mouse Blood-Forming Stem Cells (Columbia University)

    Postdoctoral Opportunity in Hematopoietic Stem Cells (Albert Einstein College of Medicine [AECOM])

    Postdoctoral Researcher – Hematopoietic and Malignant Stem Cells (Istanbul University Institute of Experimental Medicine)

    Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

    Postdoctoral Position – Hematopoietic Stem Cells (St. Jude Children’s Research Hospital)

    Postdoctoral Position – Hematopoiesis (Lund Stem Cell Center)

    Postdoctoral Appointee – Cell Cycle Regulation in Tumor Stem Cells (Rutgers University, Rutgers Cancer Institute of New Jersey)

    Postdoctoral Position – Stem Cell Biology (St. Jude Children’s Research Hospital)


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