Volume 3.37 | Sep 18

Hematopoiesis News 3.37 September 18, 2012
Hematopoiesis News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
mTOR Complex 1 Plays Critical Roles in Hematopoiesis and Pten-Loss-Evoked Leukemogenesis
The roles of the unique mechanistic target of rapamycin (mTOR) complexes (mTORCs) in hematopoiesis and leukemogenesis have not been adequately elucidated. These data delineate critical roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical strategies based on chronic mTORC1 inhibition. [Cell Stem Cell] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Monocytes-Macrophages that Express α-Smooth Muscle Actin Preserve Primitive Hematopoietic Cells in the Bone Marrow
Investigators identified a previously unknown subset of α-smooth muscle actin-positive activated monocytes and macrophages that maintain hematopoietic stem and progenitor cells and protect them from exhaustion during alarm situations. [Nat Immunol] Abstract

Recombinant IL-7/HGFβ Efficiently Induces Transplantable Murine Hematopoietic Stem Cells
Researchers used the recombinant single-chain form of a naturally occurring murine hybrid cytokine of IL-7 and the β chain of hepatocyte growth factor (rIL-7/HGFβ) in culture to induce large numbers of hematopoietic stem cells (HSCs) from multiple cell sources, including unseparated BM cells, purified HSCs, CD45- BM cells, and embryonic stem cells. [J Clin Invest] Full Article

Protein Kinase D-HDAC5 Signaling Regulates Erythropoiesis and Contributes to Erythropoietin Crosstalk with GATA1
Scientists showed that erythropoietin regulates GATA1 through protein kinase D activation, promoting histone deacetylase 5 (HDAC5) dissociation from GATA1, and subsequent GATA1 acetylation. In ex vivo studies, HDAC5-/- progenitors display enhanced entry into and passage through the erythroid lineage, as well as evidence of erythropoietin-independent differentiation. [Blood] Abstract

ERG and FLI1 Binding Sites Demarcate Targets for Aberrant Epigenetic Regulation by AML1-ETO in Acute Myeloid Leukemia
The results highlight the dual importance of ETS factors in t(8;21) leukemogenesis, both as transcriptional regulators of the oncofusion protein itself as well as proteins that facilitate AML1-ETO binding. [Blood] Abstract

Loss of p53 Exacerbates Multiple Myeloma Phenotype by Facilitating the Reprogramming of Hematopoietic Stem/Progenitor Cells to Malignant Plasma Cells by MafB
The efficiency of the MafB-induced multiple myeloma reprogramming of normal hematopoietic stem/progenitor cells to terminally differentiated malignant plasma cells is enhanced by p53 deficiency, in analogy to what happens in reprogramming to pluripotency. [Cell Cycle] Abstract

Notch Signals Contribute to Preserve the Multipotentiality of Human CD34+CD38-CD45RA-CD90+ Hematopoietic Progenitors by Maintaining T Cell Lineage Differentiation Potential
Researchers identified cord blood CD34+CD38-CD45RA-CD90+ cells as one of the earliest targets of Notch in human hematopoiesis. Upon Notch activation CD34+CD38- cells are blocked in their differentiation at the CD34+CD38-CD45RA-CD90+ stage. Notch signaling is required before lymphoid commitment to preserve T-cell potential of CD34+CD38-CD45RA-CD90+ cells. [Exp Hematol] Abstract

Identification of the Hemogenic Endothelial Progenitor and Its Direct Precursor in Human Pluripotent Stem Cell Differentiation Cultures
The authors showed that human hemogenic endothelium progenitors capable of generating definitive hematopoietic cells can be obtained from human pluripotent stem cells and identified precisely by a VE-cadherin+CD73CD235a/CD43 phenotype. [Cell Rep] Abstract

CLINICAL RESEARCH

Targeting p53 In Vivo: A First-in-Human Study with p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer
APR-246 is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. APR-246 was administered as a two-hour intravenous infusion once per day for four consecutive days in 22 patients with hematologic malignancies and prostate cancer. [J Clin Oncol] Abstract | Press Release

Autologous Blood Cell Transplantation versus HLA-Identical Sibling Transplantation for Acute Myeloid Leukemia in First Complete Remission: A Registry Study from the Center for International Blood and Marrow Transplantation Research
Investigators compared treatment related mortality, relapse, leukemia-free survival, and overall survival for acute myeloid leukemia in first complete remission receiving myeloablative HLA-matched sibling donor versus autologous peripheral blood. [Haematologica] Abstract | Full Article

T-Cell Depleted Stem-Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia: Long-Term Survival for Patients in 1st Complete Remission with a Decreased Risk of Graft-versus-Host Disease
Researchers performed a 56 patient retrospective study to evaluate T-cell depleted allogeneic hematopoietic stem cell transplantation for the treatment of acute lymphoblastic leukemia following myeloablative TBI-based therapy. [Biol Blood Marrow Transplant] Abstract

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REVIEWS

Hematopoietic Stem Cell Mobilization: Updated Conceptual Renditions
This review reports some of the more recent advances about hematopoietic stem cell mobilization, with an attempt to reconcile some of the seemingly inconsistent data in mobilization and to interject some commonalities among different mobilization regimes. [Leukemia] Abstract

Tug of War in the Hematopoietic Stem Cell Niche: Do Myeloma Plasma Cells Compete for the HSC Niche?
This review provides an overview of the bone marrow microenvironment and its involvement in normal, physiological hematopoietic stem cell (HSC) maintenance and plasma cell growth throughout multiple myeloma disease progression. [Blood Cancer J] Full Article

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INDUSTRY NEWS

Einstein Researcher Receives $10.8 Million Grant to Study Toxic Blood Reactions Caused by Hemoglobin
The National Heart, Lung, and Blood Institute, part of the National Institutes of Health, has awarded nearly $11 million to Albert Einstein College of Medicine of Yeshiva University to carry out a five-year multi-institutional study of hemoglobin toxicity that may complicate blood transfusions and reduce the effectiveness of blood substitutes. [Albert Einstein College of Medicine] Press Release

Emmaus Medical Marks Progression of Phase III Sickle Cell Disease Clinical Trial
Emmaus Medical, Inc. announced that its U.S. Phase III clinical trial to study L-Glutamine as a treatment for sickle cell disease is nearing target enrollment completion, with investigation now underway at more than 30 clinical study sites throughout the U.S. [Emmaus Medical, Inc.] Press Release | Related Video

Hybrigenics Starts Phase II Clinical Trial of Inecalcitol in Chronic Lymphocytic Leukemia
Hybrigenics announced the start of a Phase II clinical trial of oral inecalcitol in patients with chronic lymphocytic leukemia (CLL). It is an open-label trial assessing the safety and potential efficacy of inecalcitol given to CLL patients not yet requiring immuno-chemotherapy but at high risk of disease progression. [Hybrigenics] Press Release

NIH Fosters High-Risk, High-Reward Innovation at UCSF
Biomedical researchers at the University of California, San Francisco (UCSF) have won five of 51 prestigious National Institutes of Health (NIH) Director’s New Innovator awards for high-risk, high-reward research, each receiving up to $1.5 million over five years. [The University of California, San Francisco] 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 Fraunhofer Life Science Symposium Leipzig 2012
November 29-30, 2012
Leipzig, Germany

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

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Research Technologist – Media Development (STEMCELL Technologies, Inc.)


Research Technologist – Research and Development (STEMCELL Technologies, Inc.)

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


Postdoctoral Position(s) – Pharmaceutical Immunology/Hematopoietic Cell Development (National Taiwan University)

Research Associate – Quality Assurance (University of California)

Postdoctoral Position – Mouse Stem Cell Biology (University of Alabama)

Postdoctoral Position – Stem Cells and Cancer (Tsinghua University)

Scientist, Postdoctoral and Research Associate Positions (University of Miami – Sylvester Comprehensive Cancer Center)


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