Hematopoiesis News Volume 3.50 | Dec 18 2012

LABORATORY RESEARCH

Bcl11a Is Essential for Lymphoid Development and Negatively Regulates p53
Scientists report that, in the adult mouse, Bcl11a is expressed in most hematopoietic cells and is highly enriched in B cells, early T cell progenitors, common lymphoid progenitors, and hematopoietic stem cells. [J Exp Med] Abstract

Pharmacological Stabilization of HIF-1α Increases Hematopoietic Stem Cell Quiescence In Vivo and Accelerates Blood Recovery following Severe Irradiation
To investigate the effects of hypoxia on hematopoietic stem cells, the authors blocked O₂-dependent hypoxia-inducible transcription factor (HIF)-1α degradation in vivo in mice by injecting two structurally unrelated prolyl hydroxylase domain enzyme inhibitors: dimethyloxalyl glycine and FG-4497. [Blood] Abstract

A Novel Role of BMP4 in Adult Hematopoietic Stem and Progenitor Cell Homing via Smad Independent Regulation of Integrin-α4 Expression
Scientists described a novel mechanism by which BMP4 regulates homing of murine as well as human hematopoietic stem/progenitor cells. BMP4 treatment of murine bone marrow derived c-kit⁺Lin^–Sca-1⁺ (KLS) and CD150⁺CD48^–KLS cells for up to five days in vitro prevented the culture-induced loss of Integrin-α4 expression as well as homing. [Blood] Abstract

Signaling Axis Involving Hedgehog, Notch, and Scl Promotes the Embryonic Endothelial-to-Hematopoietic Transition
In differentiating mouse ES cells and mouse yolk sac cultures, addition of Indian Hedgehog (Hh) ligand increased hematopoietic progenitors, whereas chemical inhibition of Hh signaling reduced hematopoietic progenitors without affecting primitive streak mesoderm formation. [Proc Natl Acad Sci USA] Abstract

Cell of Origin Determines Clinically Relevant Subtypes of MLL-Rearranged AML
MLL-AF9 transduced single hematopoietic stem cells (HSC) or granulocyte macrophage progenitors (GMP) could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate acute myeloid leukemias (AML) in mice. [Leukemia] Abstract

Sulforaphane Induces Cell Cycle Arrest and Apoptosis in Acute Lymphoblastic Leukemia Cells
Researchers report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of acute lymphoblastic leukemia (ALL) cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. [PLoS One] Full Article | Press Release

Donor Hematopoietic Stem Cells Confer Long-Term Marrow Reconstitution by Self-Renewal Divisions Exceeding to That of Host Cells
Dormant hematopoietic stem cells are activated by microenvironmental cues of the niche in response to the injury of bone marrow. It is not clearly understood how engrafted cells respond to these cues and are involved in marrow regeneration. Scientists aimed to decipher this cellular response in a competitive environment. [PLoS One] Full Article

Avoiding Room Temperature Storage and Delayed Cryopreservation Provide Better Postthaw Potency in Hematopoietic Progenitor Cell Grafts
Researchers aimed to determine the influence on cell potency of thawed products from three sources of hematopoietic progenitor cells after prolonged storage at different temperatures before cryopreservation. [Transfusion] Abstract

CLINICAL RESEARCH

Cord-Blood Engraftment with Ex Vivo Mesenchymal-Cell Coculture
Poor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. Researchers hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells. [N Engl J Med] Abstract | Press Release

Impact of Age on Outcomes after Initial Therapy with Chemotherapy and Different Chemoimmunotherapy Regimens in Patients with Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies
Researchers examined patients enrolled onto successive first-line CALGB chronic lymphocytic leukemia trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. [J Clin Oncol] Abstract | Press Release

Phase II Trial of Sanofi JAK2 Inhibitor in Myelofibrosis Met Primary Endpoint
Sanofi announced new Phase II data showing that treatment with a novel, investigational, selective JAK2 inhibitor reduced spleen size and improved constitutional symptoms in patients with intermediate-2 or high-risk primary or secondary myelofibrosis, a hematologic malignancy with unmet medical needs. [Press release from Sanofi discussing research presented at the 54^th American Society of Hematology Annual Meeting and Exposition, Atlanta] Press Release
 
Celldex Therapeutics’ CDX-301 Safely Mobilizes Hematopoietic Cells in Phase I Study: Future Development Planned
Celldex Therapeutics, Inc. announced positive results from a Phase I multi-dose study of CDX-301 (FMS-like tyrosine kinase-3 ligand) demonstrating that CDX-301 was well-tolerated and can safely and effectively mobilize hematopoietic cell populations in healthy volunteers. The data support future development of CDX-301 in a number of indications, including hematopoietic stem cell transplant and cancer immunotherapy. [Press release from Celldex Therapeutics, Inc. discussing research presented at the 54^th American Society of Hematology Annual Meeting and Exposition, Atlanta] Press Release

Terumo BCT Launches New Clinical Trial: Red Blood Cell Exchange in Patients with Sickle Cell Disease Using the Spectra Optia® Apheresis System
Terumo BCT announced that it has begun a U.S. clinical trial to evaluate the Spectra Optia system’s new Red Blood Cell Exchange (RBCX) Protocol in patients with sickle cell disease. To date, the RBCX Protocol on the Spectra Optia system is available in other world areas for patients with sickle cell disease and for other conditions that require red blood cell exchange. [Terumo BCT] Press Release

Alliance for Regenerative Medicine Forms Tissue Engineering and Biomaterials Committee
The Alliance for Regenerative Medicine announced the formation of a Tissue Engineering and Biomaterials Committee (TEBC). The TEBC has been established to assemble the companies, academic institutions, and organizations within the Alliance for Regenerative Medicine that develop and commercialize tissue engineered and biomaterial based technologies. [Alliance for Regenerative Medicine] Press Release

BloodCenter of Wisconsin and Heartland Blood Centers to Form Strategic Alliance
BloodCenter of Wisconsin and Heartland Blood Centers, Aurora, Ill., announced they will form a strategic alliance that will offer a more comprehensive range of transfusion medicine services to hospitals. This alliance will help improve patient outcomes and create operational efficiencies. [BloodCenter of Wisconsin]
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 2013 International Cord Blood Symposium
June 7-9, 2013
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Product Quality Scientist (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Senior Lecturer – Cancer Stem Cells (The European Cancer Stem Cell Research Institute)

Postdoctoral Position – Hematopoietic Stem Cell and Leukemia Research (City of Hope Beckman Research Institute) 

Assistant Professor – Myelodysplastic Syndromes (MD Anderson Cancer Center)

Postdoctoral Fellow – Hematopoietic Stem Cells and Cancer (Tsinghua University)

Postdoctoral Fellow – Donor/Recipient Matching for Hematopoietic Stem Cell Transplantation (Cleveland Clinic Transplant Center)

Postdoctoral Research Associate Positions: Stem Cell Biology/Epigenetics (University of Wisconsin School of Medicine and Public Health)

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