Hematopoiesis News Volume 4.48 | Dec 10 2013

Gata2 Is Required for HSC Generation and Survival
Investigators found that GATA2 function is essential for the generation of hematopoietic stem cells (HSCs) during the stage of endothelial-to-hematopoietic cell transition. [J Exp Med] Abstract

Hematopoietic Stem Cells Are Acutely Sensitive to Acd Shelterin Gene Inactivation
Researchers found that mouse hematopoietic stem cells (HSCs) are acutely sensitive to inactivation of the shelterin gene Acd, encoding TPP1. Homozygosity for a hypomorphic acd allele preserved the emergence and expansion of fetal HSCs but led to profoundly defective function in transplantation assays. [J Clin Invest] Full Article

miRNomes of Hematopoietic Stem Cells and Dendritic Cells Identify miR-30b as a Regulator of Notch1
The authors examined miRNomes of mouse bone marrow hematopoietic stem cells (HSCs), immature dendritic cells (DCs), mature DCs and IL-10/NO-producing regulatory DCs by deep sequencing. They identified numerous stage-specific microRNAs (miRNAs) and histone modification in HSCs and DCs at different differentiation stages. [Nat Commun] Full Article

PLC-γ and PI3K Link Cytokines to ERK Activation in Hematopoietic Cells with Normal and Oncogenic Kras
Scientists showed that phospholipase C-γ (PLC-γ), phosphoinositide 3-kinase (PI3K), and their generated second messengers link activated cytokine receptors to Ras and signal-regulated kinase (ERK) signaling in differentiated bone marrow cells and in a cell population enriched for leukemia stem cells. [Sci Signal] Abstract

Ex Vivo Expansion of Hematopoietic Stem- and Progenitor Cells from Cord Blood in Coculture with Mesenchymal Stroma Cells from Amnion, Chorion, Wharton’s Jelly, Amniotic Fluid, Cord Blood, and Bone Marrow
Scientists investigated whether bone marrow-derived (mesenchymal stroma cells) MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton’s jelly, amniotic fluid, and cord blood (CB), which can be isolated from placental tissue which is readily available when CB is sampled. [Tissue Eng Part A] Abstract

Leukemia Cells Induce Changes in Human Bone Marrow Stromal Cells
The inflammatory cytokines IFN-gamma and TNF-alpha change the bone marrow stromal cell (BMSC) secretome and the authors hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs. [J Transl Med]
Abstract | Full Article

TIM-Family Molecules in Embryonic Hematopoiesis: Fetal Liver TIM-4lo Cells Have Myeloid Potential
Since the para-aortic region is a known site for HSC and HPC differentiation and expansion, the authors hypothesized that TIM molecules have a role in hematopoiesis. They analyzed TIM expression more precisely in chicken para-aortic region and mouse fetal liver hematopoietic cells. [Exp Hematol] Abstract

Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells
Scientists showed that transduction of c-MYC and BCL-XL into multipotent hematopoietic progenitor cells derived from pluripotent stem cells and gene overexpression enable sustained exponential self-replication of glycophorin A⁺ erythroblasts, which they term immortalized erythrocyte progenitor cells. [Stem Cell Rep]
Full Article | Press Release

CLINICAL RESEARCH

Allogeneic Hematopoietic Stem Cell Transplantation for Neuromyelitis Optica
Researchers report on durable clinical remissions after allogeneic hematopoietic stem cell transplantation in two patients suffering from severe forms of Neuromyelitis Optica. [Ann Neurol] Abstract

Hematopoietic Stem Cell Transplantation in Children and Young Adults with Secondary Myelodysplastic Syndrome and Acute Myeloid Leukemia following Aplastic Anemia
Investigators evaluated the outcome of hematopoietic stem cell transplantation in 17 children and young adults with secondary myelodysplastic syndrome and acute myeloid leukemia following childhood aplastic anemia. [Biol Blood Marrow Transplant] Abstract

Cryopreserved Stem Cell Products Containing Dimethyl Sulfoxide Lead to Activation of the Coagulation System without Any Impact on Engraftment
Little is known on direct hemostatic changes in recipients of hematopoietic stem cell transplantation (HSCT) immediately after dimethyl sulfoxide administration. Researchers aimed to measure hemostatic changes during HSCT. [Transfusion] Abstract

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Pioneering Advances in Stem Cell Transplantation Strategies Show Promise to Improve Availability, Success of Lifesaving Procedure
Hematopoietic stem cell transplantation, once considered an effective yet risky alternative to drug therapy for blood cancer, has become more accessible and successful in a wide range of patients as a result of major advances in transplant strategies and technologies. [Press release from the American Society of Hematology discussing research presented at 55th American Society of Hematology Annual Meeting and Exposition, New Orleans] Press Release

Flipping a Gene Switch Reactivates Fetal Hemoglobin, May Reverse Sickle Cell Disease
Hematology researchers at The Children’s Hospital of Philadelphia have manipulated key biological events in adult blood cells to produce a form of hemoglobin normally absent after the newborn period. Because this fetal hemoglobin is unaffected by the genetic defect in sickle cell disease, the cell culture findings may open the door to a new therapy for the debilitating blood disorder. [Press release from EurekAlert! discussing research presented at the 55th annual meeting of the American Society of Hematology, New Orleans] Press Release

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Ambit Biosciences Provides Regulatory Update Following FDA Meeting Regarding Quizartinib (AC220)
Ambit Biosciences announced a regulatory update after receiving feedback from the U.S. Food and Drug Administration (FDA) on the development of quizartinib (AC220), the company’s lead drug candidate, for the treatment of relapsed/refractory acute myeloid leukemia (AML). Based on feedback from the FDA, the company continues to move forward with its baseline plan to conduct a randomized, controlled Phase III clinical trial in relapsed/refractory FLT3-ITD positive AML patients with an overall survival endpoint as the basis for the potential initial approval of quizartinib. [Ambit Biosciences] Press Release

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)

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Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

Postdoctoral Fellow – Molecular Basis of Clonal Evolution in Leukemia (Northwestern University)

Postdoctoral Positions – Hematopoietic Stem Cell Physiology (University of Michigan)

Postdoctoral Position – Hematopoietic Stem Cell Research (Lund Stem Cell Center)

Director of Sponsored Programs (Wake Forest Institute for Regenerative Medicine)

Adult Stem Cell Transplant Physician (John Theurer Cancer Center)

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

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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