Volume 5.10 | Mar 18

Hematopoiesis News 5.10 March 18, 2014
Hematopoiesis News
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Csnk1a1 Inhibition Has p53-Dependent Therapeutic Efficacy in Acute Myeloid Leukemia
Investigators evaluated whether D4476, a casein kinase 1 (Csnk1) inhibitor, would exhibit selective antileukemic effects. Treatment of leukemia stem cells (LSCs) with D4476 showed highly selective killing of LSCs over normal hematopoietic stem and progenitor cells. [J Exp Med] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection
Researchers revealed that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. [Cell Host Microbe] Abstract | Graphical Abstract | Press Release

Inhibition of Endothelial ERK Signaling by Smad1/5 Is Essential for Hematopoietic Stem Cell Emergence
Scientists showed that interplay of Smad1/5 and ERK signaling is essential for hemogenic endothelium-based hematopoietic stem cell emergence. Smad1/5 directly inhibits erk expression through recruiting HDAC1 to and inducing de-acetylation of the erk promoter in endothelial cells. [Nat Commun] Abstract

Mechanism Governing a Stem Cell-Generating cis-Regulatory Element
Scientists describe the targeted deletion of the Gata2 -3.9 switch site and mechanistically compare the -3.9 site with other GATA switch sites. The -3.9-/- mice were viable and exhibited normal Gata2 expression and steady-state hematopoiesis in the embryo and adult. [Proc Natl Acad Sci USA] Abstract

Total Body Irradiation Causes Long-Term Mouse BM Injury via Induction of HSC Premature Senescence in an Ink4a- and Arf-Independent Manner
Hematopoietic stem cell (HSC) defects were associated with significant increases in production of reactive oxygen species, expression of p16Ink4a and Arf mRNA, and senescence-associated β-galacotosidase activity, but not with telomere shortening or increased apoptosis, suggesting that total body irradiation induces residual bone marrow (BM) injury via induction of HSC premature senescence. [Blood] Abstract

Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity
Scientists hypothesized that overexpression of microRNA-126 in the hematopoietic compartment could protect the kidney against Ischemia/reperfusion injury via preservation of microvascular integrity. [J Am Soc Nephrol] Abstract

Autophagy Is a Survival Mechanism of Acute Myeloid Leukemia Precursors during Dual mTORC2/mTORC1 Targeting
Researchers examined whether induction of autophagy is a mechanism of leukemic cell resistance to dual mTORC1/mTORC2 inhibitors in acute myeloid leukemia leukemic progenitors. [Clin Cancer Res] Abstract

Variable Correction of Artemis Deficiency by I-Sce1-Meganuclease-Assisted Homologous Recombination in Murine Hematopoietic Stem Cells
Investigators used the DNA double-strand breaks introduced by the site-specific endonuclease I-Sce1 as a means of increasing homologous recombination of an exogenous DNA template in murine hematopoietic stem cells. [Gene Ther] Abstract


Effects of Hematopoietic Stem Cell Transplantation on Acyl-CoA Oxidase Deficiency: A Sibling Comparison Study
Researchers describe the natural history of clinical symptoms and brain imaging in two siblings with acyl-CoA oxidase deficiency, including the younger sibling’s response to allogeneic unrelated donor hematopoietic stem cell transplantation. [J Inherit Metab Dis] Abstract

Plerixafor Added to G-CSF-Supported Paclitaxel-Ifosfamide-Cisplatin Salvage Chemotherapy Enhances Mobilization of Adequate Numbers of Hematopoietic Stem Cells for Subsequent Autografting in Hard-to-Mobilize Patients with Relapsed/Refractory Germ-Cell Tumors: A Single-Center Experience
Investigators applied plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) after salvage chemotherapy in ‘poor’ mobilizers with relapsed/refractory germ-cell tumors for high-dose chemotherapy plus autologous hematopoietic cell transplantation. [Anticancer Drugs] Abstract

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Chromatin Modifiers and the Promise of Epigenetic Therapy in Acute Leukemia
The authors discuss the range of recurrent, somatic mutations in epigenetic modifiers found in leukemia and how these modifiers relate to the classical leukemogenic pathways that lead to impaired cell differentiation and aberrant self-renewal and proliferation. [Leukemia] Full Article

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STEMSOFT Announces Release of New BMT Clinic Software Solution
STEMSOFT™ Software Inc. announced the release of a new BMT cellular therapy transplant software solution, STEMSOFT CLINIC. This new system efficiently manages all patient and donor information in one location complete with an available BMT registry submission and retrieval process for all available forms using the CIBMTR AGNIS system. [STEMSOFT™ Software Inc.] Press Release

NeoStem Reports Fourth Data Safety Monitoring Board Review of PreSERVE AMI Trial
NeoStem, Inc. announced that the Data Safety Monitoring Board recommended continuing the PreSERVE AMI Phase II clinical trial following a fourth interim data and safety review. [NeoStem, Inc.] Press Release

ATL1102 for Stem Cell Mobilization Trial Commencement
Antisense Therapeutics advised that it has commenced dosing in its Phase I Stem Cell Mobilization Human Proof of Concept trial of ATL1102, the company’s second generation antisense drug targeting the VLA-4 receptor. The trial will assess the safety, tolerability and effect of ATL1102 on the release of hematopoietic stem cells into the blood when dosed alone and in combination with an existing therapy (Granulocyte Colony Stimulating Factor). [PR Newswire Association LLC] Press Release

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Alliance for Regenerative Medicine Announces Introduction of Regenerative Medicine Promotion Act of 2014 in the Senate
The Alliance for Regenerative Medicine announced the introduction of the Regenerative Medicine Promotion Act of 2014 in the U.S. Senate and expressed appreciation for the efforts of its lead sponsors, Senators Barbara Boxer (D-CA) and Mark Kirk (R-IL). [Alliance for Regenerative Medicine] Press Release

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)
NEW Transtem Patient 2014
March 19, 11:00 AM (CDT in US)

NEW International Society for Laboratory Hematology 2014
May 15-17, 2014
The Hague, Netherlands

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NEW Postdoctoral Position – Immunotherapies for Cancer Based on Genetic Engineered T Lymphocytes and/or Hematopoietic Stem Cells (Roswell Park Cancer Institute)

Postdoctoral Fellow – Mammalian Hematopoietic and Erythroid Development (The Icahn School of Medicine at Mount Sinai)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Position – Human Stem Cell Biology and Hematopoiesis (Johns Hopkins University School of Medicine)

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

Postdoctoral Position – Genes that Regulate Hematopoietic Stem Cells (University of Chicago)

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

Postdoctoral Position – Hematopoietic Stem Cell Physiology and Bone Marrow Failure (University of Michigan)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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