Hematopoiesis News Volume 6.29 | Jul 28 2015

Activation of OCT4 Enhances Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem and Progenitor Cells by Regulating HOXB4 Expression
Investigators present their unexpected finding that OCT4 is involved in the enhancement of cytokine-induced expansion capabilities of human cord blood hematopoietic stem cells. [Leukemia] Abstract

Runx1 Repression by Histone Deacetylation Is Critical for Setbp1-Induced Mouse Myeloid Leukemia Development
Scientists showed that Setbp1 overexpression in mouse bone marrow progenitors through retroviral transduction is capable of initiating leukemia development in irradiated recipient mice. [Leukemia] Abstract

Mitochondrial Metabolism in Hematopoietic Stem Cells Requires Functional FOXO3
The authors identified the transcription factor FOXO3 as a new regulator of metabolic adaptation of hematopoietic stem cells (HSC). Reactive oxygen species are elevated in Foxo3^-/- HSC that are defective in their activity. [EMBO Rep] Abstract

PRC2 Inhibition Counteracts the Culture-Associated Loss of Engraftment Potential of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells
Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential, scientists profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells. [Sci Rep] Full Article

Fetal Hematopoietic Stem Cells Express MFG-E8 during Mouse Embryogenesis
The authors investigated milk fat globule-EGF-factor 8 protein (MFG-E8) expression in multiple hematopoietic tissues at different stages of mouse embryogenesis. Using immunohistochemistry, they showed that MFG-E8 was specifically expressed in CD34⁺ hematopoietic stem cells at all hematopoietic sites, including the yolk sac, aorta-gonad-mesonephros region, placenta and fetal liver, during embryogenesis. [Exp Mol Med] Full Article

Deficiency in Aryl Hydrocarbon Receptor (AHR) Expression throughout Aging Alters Gene Expression Profiles in Murine Long-Term Hematopoietic Stem Cells
Scientists sorted the most primitive population of hematopoietic stem cells (HSCs) with the highest stem cell potential from 18-month-old AhR-null-allele (AhR-KO) and WT mice and analyzed gene expression using microarray to determine alterations in gene expression and cell signaling networks in HSCs that could potentially contribute to the aging phenotype of AhR-KO mice. [PLoS One] Full Article

Hematopoietic Knockdown of PPARdδ Reduces Atherosclerosis in LDLR^-/- Mice
Researchers employed a microRNA approach to knock down PPARδ (peroxisome proliferator-activated receptor delta) expression in bone marrow cells followed by transplantation of the cells into LDLR^-/- mice. [Gene Ther] Abstract

CLINICAL RESEARCH

Long-Term Sustained Disease Control in Patients with Mantle Cell Lymphoma with or without Active Disease after Treatment with Allogeneic Hematopoietic Cell Transplantation after Nonmyeloablative Conditioning
Investigators examined the outcomes of 70 patients with mantle cell lymphoma and included extended follow-up for the 33 initial patients. Grafts were obtained from human leukocyte antigen (HLA)-matched, related donors, unrelated donors, and HLA antigen-mismatched donors. [Cancer] Abstract

Favorable Outcome of Haploidentical Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Multicenter Study in Southwest China
Investigators analyzed the clinical outcomes of 82 Philadelphia chromosome-positive acute lymphoblastic leukemia patients who underwent haploidentical hematopoietic stem cell transplantation (HSCT) or HLA-matched HSCT. [J Hematol Oncol] Full Article

Treatment with PF-04449913, an Oral Smoothened Antagonist, in Patients with Myeloid Malignancies: A Phase I Safety and Pharmacokinetics Study
Investigators undertook an open-label, dose-finding, standard 3+3 design Phase I study of PF-04449913 in adult patients with acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic syndrome, or myelofibrosis who were refractory, resistant, or intolerant to previous treatments, at three centers in the USA and one in Italy. [Lancet Haematol] Abstract | Press Release

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Revolade^® Recommended by CHMP for EU Approval to Treat Patients with Severe Aplastic Anemia, a Serious Blood Disorder
Ligand Pharmaceuticals Incorporated announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for Revolade^® (eltrombopag), a Novartis product, for the treatment of adult patients with acquired severe aplastic anemia who were either refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for hematopoietic stem cell transplantation. [Ligand Pharmaceuticals Incorporated] Press Release

University of Toronto to Transform Regenerative Medicine Thanks to Historic $114 Million Federal Grant
The University of Toronto is set to cement its position as one of the world’s leading centers for the design and manufacture of cells, tissues and organs that can be used to treat degenerative disease, thanks to a $114-million grant from the federal government. [University of Toronto] Press Release

CDRD & OICR Team up to Advance Cutting-Edge New Cancer Treatments
Two of Canada’s leading drug research and commercialization centers have announced a call for proposals to help bring new cancer treatments to patients through collaborative technology-development projects from academic investigators across Canada. [Center for Drug Research and Development (CDRD)] Press Release

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NEW Postdoctoral Position – Hematopoietic Stem and Progenitor Cell Assays (Weill Cornell Medical School)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Biology (Editas Medicine)

PhD Position – Drug Releasing, Nanostructured Biomaterials for Adult Stem Cells (Karlsruhe Institute of Technology)

Postdoctoral Position – Splicing in Hematopoiesis (Northwestern University)

Clinical Research Coordinator – Chronic Lymphocytic Leukemia (Fred Hutchinson Cancer Research Center)

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

Postdoctoral Position – Hematopoietic Stem Cell and Hematologic Malignancy (University of Kentucky College of Medicine)

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