Hematopoiesis News Volume 5.19 | May 20 2014

Wnt Signaling Controls the Specification of Definitive and Primitive Hematopoiesis from Human Pluripotent Stem Cells
Scientists showed that both hematopoietic programs transition through hemogenic endothelial intermediates and develop from KDR⁺CD34^–CD144^– progenitors that are distinguished by CD235a expression. [Nat Biotechnol] Abstract

Lysophosphatidic Acid Acts as a Nutrient-Derived Developmental Cue to Regulate Early Hematopoiesis
Scientists showed that lysophosphatidic acid (LPA), a signaling molecule derived from phosphatidylcholines, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 or autotoxin, a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. [EMBO J] Abstract

Loss of SPARC Protects Hematopoietic Stem Cells from Toxicity of Repeated Cycles of Chemotherapy by Accelerating Their Return to Quiescence
The authors demonstrate that SPARC-deficient mice display higher resistance to serial treatment with the chemotherapeutic agent 5-fluorouracil. Using straight and reverse chimeras, they further showed that this protective effect is not due to a role of SPARC in hematopoietic stem cells, but rather due to its function in the bone marrow niche. [Blood] Abstract

Effector-Mediated Eradication of Precursor B Acute Lymphoblastic Leukemia with a Novel Fc-Engineered Monoclonal Antibody Targeting the BAFF-R
Investigators examined therapeutic targeting of precursor B acute lymphoblastic leukemia (pre-B ALL) based on the presence of the B-cell activating factor receptor (BAFF-R). Mouse pre-B ALL cells lacking BAFF-R function had comparable viability and proliferation to wild-type cells, but were more sensitive to drug treatment in vitro. [Mol Cancer Ther] Abstract | Press Release

Linkage between Dendritic and T Cell Commitments in Human Circulating Hematopoietic Progenitors
Investigators enumerated and characterized conventional dendritic cell (DC) and plasmacytoid DC precursors in association with T cell and thymus-derived types of NK cell precursors among CD34⁺ hematopoietic progenitor cells circulating in human peripheral blood. [J Immunol] Abstract

Regulation of Embryonic Hematopoiesis by a Cytokine-Inducible SH2 Domain Homolog in Zebrafish
Injection of morpholinos targeting Cytokine-inducible SH2 domain-containing protein a (cish.a), but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a two- to threefold increase in erythrocytic markers. [J Immunol] Abstract

The Adult Livers of Immunodeficient Mice Support Human Hematopoiesis: Evidence for a Hepatic Mast Cell Population that Develops Early in Human Ontogeny
Scientists sought to model human adult-liver hematopoiesis by transplantation of fetal and neonatal hematopoietic stem cells into adult immunodeficient mice. Livers were found to be engrafted with human cells consisting primarily of monocytes and B-cells with lesser contributions by erythrocytes, T-cells, NK-cells and mast-cells. [PLoS One] Full Article

CLINICAL RESEARCH

T-Cell Infiltration of the Human Bone Marrow during Acute Graft-versus-Host Disease Is Associated with Impaired B-Cell Reconstitution and Function after Allogeneic-HSCT
Investigators analyzed reconstitution kinetics of B-cell subsets in adult leukemic patients within six months after allogeneic-hematopoietic stem cell transplantation (HSCT). B-cell deficiency existed already pre-transplant and was aggravated post-transplant. [Blood] Abstract

Second Hematopoietic SCT Using HLA-Haploidentical Donors in Patients with Relapse of Acute Leukemia after a First Allogeneic Transplantation
Haploidentical haematopoietic SCT (HSCT) using T-cell-replete grafts and post-transplant high-dose CY has found increasing acceptance. The authors evaluated the feasibility and outcome of this strategy as second HSCT incorporating donor change for acute leukemia relapse after a first allogeneic transplantation. [Bone Marrow Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

Karyopharm Receives Orphan Drug Designation for Acute Myeloid Leukemia (AML)
Karyopharm Therapeutics Inc. announced that that its lead drug candidate, Selinexor (KPT-330) oral, has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of AML. [Karyopharm Therapeutics Inc.] Press Release

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Postdoctoral Fellow – Mammalian Hematopoietic and Erythroid Development (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Regulation of Cytokine Receptor Signaling in Hematopoietic Stem Cells (University of Pennsylvania School of Medicine)

Postdoctoral Positions – New Models of Hematopoiesis and Hematopoietic Disorders (Icahn School of Medicine at Mount Sinai)

Postdoctoral Researcher – Cancer Genomics (University of Chicago)

Postdoctoral Fellow in Cardiovascular Immunology / Hematology (Massachusetts General Hospital)

Postdoctoral Associate – Hematopoietic Differentiation (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellowship – Hematology, Immunology, Cancer Therapeutics (Nationwide Children’s Hospital)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Research Technologist – hPSC (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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