Volume 5.36 | Sep 23

Hematopoiesis News 5.36 September 23, 2014
Hematopoiesis News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Pyrimidoindole Derivatives Are Agonists of Human Hematopoietic Stem Cell Self-Renewal
Investigators identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least six months in immunocompromised mice. [Science] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of del(5q) MDS
Investigators generated a murine model with conditional inactivation of casein kinase 1A1 gene (Csnk1a1) and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic stem cell failure. [Cancer Cell] Abstract | Graphical Abstract

WASH Is Required for the Differentiation Commitment of Hematopoietic Stem Cells in a c-Myc-Dependent Manner
Scientists show that conditional Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) deletion in the hematopoietic system causes defective blood production of the host, leading to severe cytopenia and rapid anemia. [J Exp Med] Abstract

Discrete Notch Signaling Requirements in the Specification of Hematopoietic Stem Cells
Researchers demonstrate that three of the four Notch receptors are independently required for the specification of hematopoietic stem cells (HSCs) in the zebrafish. The orthologs of the murine Notch1 receptor, Notch1a and Notch1b, are each required intrinsically to fate HSCs, just prior to their emergence from aortic hemogenic endothelium. [EMBO J] Abstract

Quiescent Hematopoietic Stem Cells with Short Telomeres Accumulate Genomic Damage but Are Blocked from Hematopoietic Activation by Senescence and Apoptosis
Scientists show that telomere shortening results in DNA damage accumulation and gene expression changes in quiescent hematopoietic stem cells (HSCs) of aged mice. Upon activation, a subset of HSCs with elevated levels of DNA damage and p16 expression is blocked from cell cycle entry and apoptosis is induced in HSCs entering cell cycle. [Blood] Abstract

Requirement for Ssbp2 in Hematopoietic Stem Cell Maintenance and Stress Response
Investigators provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells in vivo. [J Immunol] Abstract

Prep1 (pKnox1) Regulates Mouse Embryonic HSC Cycling and Self-Renewal Affecting the Stat1-Sca1 IFN-Dependent Pathway
Scientists demonstrate that Prep1 regulates the number of hematopoietic stem cells in fetal livers, their clonogenic potential and their ability to de novo generate the hematopoietic system in ablated hosts. [PLoS One] Full Article

Leukemic Stem Cell Frequency: A Strong Biomarker for Clinical Outcome in Acute Myeloid Leukemia
The nature of the putative leukemic stem cells and normal hematopoietic stem cells, present in the same patient’s bone marrow, was demonstrated in eight patients by the presence or absence of molecular aberrancies and/or leukemic engraftment in NOD-SCID IL-2Rγ-/- mice. [PLoS One] Full Article

CLINICAL RESEARCH

Bone Marrow Graft as a Source of Allogeneic Hematopoietic Stem Cells in Patients Undergoing a Reduced Intensity Conditioning Regimen
In an attempt to reduce the incidence of chronic GvHD after reduced-intensity conditioning, investigators used BM instead of PBSC and added melphalan 100 mg/m2 to the classical association of fludarabine, 30 mg/m2/day for three days and TBI, 200 cGy. [Bone Marrow Transplant] Abstract

Impact of Pre-Transplantation Disease Burden on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Refractory and Relapsed AML: A Single-Center Study
Patients with refractory or relapsed acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation, were retrospectively assessed to evaluate the effect of disease burden on outcomes and to identify predictive variables. [Leuk Lymphoma] Abstract

Treosulfan-Based Conditioning Regimens for Allogeneic HSCT in Children with Acute Lymphoblastic Leukemia
Researchers retrospectively studied toxicity and outcome of 71 pediatric patients with acute lymphoblastic leukemia undergoing hematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. [Ann Hematol] Abstract

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REVIEWS
Functional Significance of Mononuclear Phagocyte Populations Generated through Adult Hematopoiesis
The authors focused on mononuclear phagocytes that comprise the nonresident monocyte/macrophage populations in the body. Key features of monocyte differentiation are presented, focusing primarily on the developmental hierarchy that is established through this process, the markers used to identify discrete cell populations, and novel, functional attributes of these cells. [J Leukoc Biol] Abstract

Biomimetic Nanoparticles for siRNA Delivery in the Treatment of Leukemia
This review described current treatments for leukemia and highlights the potential of leukemic fusion genes as therapeutic targets for RNA interference (RNAi). In addition, the design of biomimetic nanoparticles which are capable of responding to the physiological environment of leukemia and their potential to advance RNAi therapeutics to the clinic was critically evaluated. [Biotechnol Adv] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
 
SCIENCE NEWS
BioLineRx Presents Positive Preclinical Results in Treatment for AML Patients with FLT3 Mutations
BioLineRx Ltd. announced the presentation of positive preclinical results of its BL-8040 cancer therapy platform, as a novel treatment for a sub-population of acute myeloid leukemia (AML patients with FLT3 mutations). [Press release from BioLineRx Ltd. at the Society of Hematologic Oncology (SOHO) 2014 Annual Meeting, Houston] Press Release

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INDUSTRY NEWS
Novel Drug Targeting Leukemia Cells Enters Clinical Trial
Researchers have launched a Phase I human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia, the most common form of blood cancer in adults. [University of California, San Diego] Press Release

European Commission Grants Marketing Authorization for Gilead’s Zydelig® (Idelalisib) for the Treatment of Chronic Lymphocytic Leukemia and Follicular Lymphoma
Gilead Sciences, Inc. announced that the European Commission has granted marketing authorization for Zydelig®, 150 mg tablets, a first-in-class oral treatment for two incurable blood cancers – chronic lymphocytic leukemia and follicular lymphoma. [Gilead Sciences, Inc.] 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 XXII Congress of the European Society of Gene and Cell Therapy (ESGCT)
October 23-26, 2014
The Hague, The Netherlands

NEW CellTech India 2015
March 2-3, 2015
Bangalore, India

Visit our events page to see a complete list of events in the hematopoiesis community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Position – Cell Signaling in Hematopoietic Stem Cells (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Position – Regenerative Effects of Some Mutations on Hematopoietic Stem Cells (Istanbul University Institute of Experimental Medicine)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant – Oxford)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant – Leeds)

Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

PhD Position – Stem Cells for Anti-Cancer Vγ9Vδ2 T Cells (Free University of Brussels)

Stem Cell Biology Program Director (Blood Research Institute of BloodCenter of Wisconsin)

Assistant or Associate Professor – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Associate – Cancer, Stem Cells, and Immunity Focusing on Membrane Proteins and Signaling Pathways (UT Southwestern Medical Center)

Postdoctoral Positions – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)


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