Hematopoiesis News Volume 4.34 | Sep 3 2013

The Murine Long-Term Multi-Lineage Renewal Marrow Stem Cell Is a Cycling Cell
Although hematopoietic stem cell (HSC) cycle status has long been the subject of scrutiny, virtually all marrow stem cell research has been based on studies of highly purified HSCs. Investigators explored the cell cycle status of marrow stem cells in un-separated whole bone marrow. [Leukemia] Abstract

A Novel Role for Factor VIII and Thrombin/Par1 in Regulating Hematopoiesis and Its Interplay with the Bone Structure
Analysis of hematopoietic stem cells (HSC) in Factor VIII Knock Out (FVIII-KO) mice revealed a novel regulatory role for the coagulation cascade in hematopoiesis. Thus, HSC in FVIII-KO mice had reduced proportions of CD34^low cells within Lin^–Sca⁺Kit⁺ progenitors, and exhibited reduced long term repopulating capacity as well as hyper G-CSF induced mobilization. [Blood] Abstract

Prostaglandin-Modulated Umbilical Cord Blood Hematopoietic Stem Cell Transplantation
Umbilical cord blood contains an inherently limited hematopoietic stem cell (HSC) count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E₂ (dmPGE₂) was previously identified to be a critical regulator of HSC homeostasis and researchers hypothesized that a brief ex vivo modulation with dmPGE₂ could improve patient outcomes by increasing the “effective dose” of HSCs. [Blood] Abstract

A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility
A phosphoproteomics approach to the analysis of a hematopoietic progenitor cell line treated with CXCL12 and the Rac 1 and 2 inhibitor NSC23766 was employed to objectively discover novel mechanisms for regulation of stem cells in normal and malignant hematopoiesis. The proteomic datasets identified new aspects of CXCL12-mediated signaling and novel features of stem cell regulation. [Mol Cell Proteomics] Abstract

p27^kip1 Maintains a Subset of Leukemia Stem Cells in the Quiescent State in Murine MLL-Leukemia
To investigate whether p27 plays a role in the pathogenesis of mixed-lineage leukemia (MLL), investigators examined the effects of p27 deletion (p27^-/-) on MLL-AF9-induced murine acute myeloid leukemia (AML) development. HOXA9/MEIS1-induced, p27 wild-type (p27^+/+) and p27^-/- AML were studied in parallel as controls. [Mol Oncol] Abstract

Modification of Hematopoietic Stem/Progenitor Cells with CD19-Specific Chimeric Antigen Receptors as a Novel Approach for Cancer Immunotherapy
Researchers propose gene transfer to hematopoietic stem/progenitor cells as a novel approach to deliver the CD19-specific Chimeric Antigen Receptor, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. [Hum Gen Ther] Abstract

LDL Cholesterol Modulates Human CD34+ HSPCs through Effects on Proliferation and the IL-17 G-CSF Axis
In mice, high cholesterol levels mobilize hematopoietic stem/progenitor cells (HSPCs) into the bloodstream, and promote their differentiation to granulocytes and monocytes. Scientists determined how cholesterol levels affect HSPC quantity in humans. [PLoS One] Full Article

CLINICAL RESEARCH

Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia in Remission: Comparison of Intravenous Busulfan plus Cyclophosphamide (Cy) versus Total-Body Irradiation plus Cy as Conditioning Regimen-A Report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Researchers performed a retrospective registry-based study comparing outcomes of patients with acute myelogenous leukemia in first or second remission after allogeneic stem-cell transplantation from sibling donors who underwent intravenous busulfan/Cy or Cy/total-body irradiation conditioning. [J Clin Oncol] Abstract

Tandem Autologous/Allogeneic Hematopoietic Stem Cell Transplantation in First Line High Risk Multiple Myeloma Patients: Evolving Strategies with the Immunomodulating Drugs
Investigators prospectively evaluated in high risk myeloma patients the efficacy and toxicity of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) followed by reduced intensity conditioning and allogeneic (allo)-HSCT with bortezomib and donor lymphocyte infusions introduction after allo-HSCT. [Exp Hematol] Abstract

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Stem Cell Agency Awards More than $40 Million in New Research Grants
The California Institute for Regenerative Medicine’s governing board, the Independent Citizens Oversight Committee, approved $40 million in funding for researchers at 10 institutions including Stanford, UCLA, UC San Diego, Human BioMolecular Research Institute, Cedars-Sinai Medical Center, The Gladstone Institutes, Sanford-Burnham Medical Research Institute, The Salk Institute, Numerate, Inc. and UC Irvine as part of its Early Translational IV Research awards. [California Institute for Regenerative Medicine] Press Release

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

Postdoctoral Fellow – Gene Expression and Regulation in Stem Cell Biology (University of Texas Medical School)

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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