Hematopoiesis News Volume 5.04 | Feb 4 2014

Erythropoietin Guides Multipotent Hematopoietic Progenitor Cells toward an Erythroid Fate
Investigators observed that high systemic levels of erythropoietin reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. [J Exp Med] Abstract

HSC Commitment-Associated Epigenetic Signature Is Prognostic in Acute Myeloid Leukemia
The authors delineated DNA cytosine methylation profiles of highly purified long-term hematopoietic stem cells (HSC), short-term HSC, common myeloid progenitors, and megakaryocyte-erythrocyte progenitors from the BM of healthy human individuals. They showed that an epigenetic stem cell commitment-specific signature is highly prognostic for overall survival of patients with acute myeloid leukemia. [J Clin Invest]
Full Article | Press Release

Attenuation of MicroRNA-126 Expression that Drives CD34+38- Stem/Progenitor Cells in Acute Myeloid Leukemia Leads to Tumor Eradication
To address the need for therapeutic targets in leukemic stem-like cells (LSC), researchers compared microRNA expression patterns in highly enriched healthy CD34+CD38- hematopoietic stem cells, CD34+CD38- LSC and CD34+CD38+ leukemic progenitors, all derived from the same patients’ bone marrow specimens. [Cancer Res] Abstract

In Vivo Evidence for an Instructive Role of Fms-Like Tyrosine Kinase-3 (FLT3) Ligand in Hematopoietic Development
In vivo administration of FLT3 ligand (FLT3L) promotes expansion of progenitors with combined myeloid and lymphoid potential. To investigate further the role of this cytokine in hematopoietic development, researchers generated transgenic mice expressing high levels of human FLT3L. [Haematologica] Abstract | Full Article

Hypercholesterolemia-Induced Priming of Hematopoietic Stem and Progenitor Cells Aggravates Atherosclerosis
Scientists investigated how hypercholesterolemia affects hematopoietic stem and progenitor cell (HSPC) biology and atherosclerosis. Hypercholesterolemia induced loss of HSPC quiescence, characterized by increased proliferation and expression of cyclin B₁, C₁, and D₁, and a decreased expression of Rb, resulting in a 3.6- fold increase in the number of HSPCs in hypercholesterolemic Ldlr^−/− mice. [FASEB J] Abstract

Frozen Cord Blood Hematopoietic Stem Cells Differentiate into Higher Numbers of Functional Natural Killer Cells In Vitro than Mobilized Hematopoietic Stem Cells or Freshly Isolated Cord Blood Hematopoietic Stem Cells
Investigators compared the capacity of frozen or freshly isolated umbilical cord blood hematopoietic stem cells and frozen mobilized peripheral blood hematopoietic stem cells to generate natural killer cells in vitro. [PLoS One] Full Article

Lethal Giant Larvae 1 Tumor Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukemia
In lethal giant larvae-negative (Lgl1^-/-) mice, the authors analyzed the development of hematopoietic malignancies either alone, or in the presence of common oncogenic lesions. They showed that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. [PLoS One] Full Article

Gadd45a Deletion Aggravates Hematopoietic Stem Cell Dysfunction in ATM-Deficient Mice
Researchers report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ataxia telangiectasia mutated-deficient (ATM^-/-) mice. Instead, ATM and Gadd45a double knockout hematopoietic stem cells (HSCs) exhibited an aggravated defect in long-term self-renewal capacity compared to ATM^-/- HSCs in HSC transplantation experiments. [Protein Cell] Full Article

CLINICAL RESEARCH

Phosphatidylinositol-3-Kinase Delta Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma
In this single-group, open-label, Phase II study, 125 patients with indolent non-Hodgkin’s lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within six months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. [N Engl J Med] Abstract | Press Release

Therapy-Related Acute Myeloid Leukemia and Myelodysplastic Syndromes in Patients with Hodgkin Lymphoma: A Report from the German Hodgkin Study Group
Researchers retrospectively analyzed incidence, outcome and risk factors for the development of therapy-related acute myeloid leukemia and myelodysplastic syndromes after Hodgkin lymphoma. [Blood] Abstract

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Stem Cell Agency Funds More than $66 Million in Research Including New Genomics Initiative
A team bringing together experts and investigators from seven different major California institutions has been awarded $40 million to create a new Center of Excellence in Stem Cell Genomics, by California’s stem cell agency, the California Institute for Regenerative Medicine. [California Institute for Regenerative Medicine]
Press Release

TotipotentRX and ThermoGenesis Achieve Bone Marrow Stem Cell Transplant Milestone
ThermoGenesis Corp. and TotipotentRX Corporation announced the TotipotentRX cellular therapy clinical team in partnership with Fortis Healthcare, Gurgaon (New Delhi) has achieved its 20^th pediatric bone marrow transplant. [ThermoGenesis Corp.] Press Release

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NEW Assistant Professorship – Hematopoietic Stem Cells and Microenvironment (University of Zurich)

NEW Lab Technologist – Human Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Hematopoietic Stem Cell and Leukemia Research (City of Hope)

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

Research Associate – Normal & Leukemic Stem Cells (King’s College London)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Scientific Affairs Coordinator (American Society of Hematology)

Postdoctoral Position – Erythroid and Myeloid Differentiation of Hematopoietic Stem Cells (Imagine Institute)

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