Volume 5.40 | Oct 21

Hematopoiesis News 5.40 October 21, 2014
Hematopoiesis News
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TOP STORY
Megakaryocytes Maintain Homeostatic Quiescence and Promote Post-Injury Regeneration of Hematopoietic Stem Cells
Scientists report a dichotomous role of megakaryocytes (MKs) in both maintaining hematopoietic stem cell (HSC) quiescence during homeostasis and promoting HSC regeneration after chemotherapeutic stress. They show that MKs are physically associated with HSCs in the bone marrow of mice and that MK ablation led to activation of quiescent HSCs and increased HSC proliferation. [Nat Med] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Megakaryocytes Regulate Hematopoietic Stem Cell Quiescence through CXCL4 Secretion
Researchers show that megakaryocytes (MKs) can directly regulate hematopoietic stem cell (HSC) pool size in mice. Three-dimensional whole-mount imaging revealed that endogenous HSCs are frequently located adjacent to MKs in a nonrandom fashion. [Nat Med] Abstract

Myeloproliferative Neoplasms Can Be Initiated from a Single Hematopoietic Stem Cell Expressing JAK2-V617F
Researchers demonstrate by limiting dilution and single-cell transplantations that myeloproliferative neoplasm (MPN) disease, manifesting either as erythrocytosis or thrombocytosis, can be initiated clonally from a single cell carrying JAK2-V617F. However, only a subset of mice reconstituted from single hematopoietic stem cells displayed MPN phenotype. [J Exp Med] Abstract

Dynamic Shifts in Occupancy by TAL1 Are Guided by GATA Factors and Drive Large-Scale Reprogramming of Gene Expression during Hematopoiesis
Scientists combined ChIP-seq and RNA-seq data in six mouse cell types representing a progression from multilineage precursors to differentiated erythroblasts and megakaryocytes. They found that sites of occupancy shift dramatically during commitment to the erythroid lineage, vary further during terminal maturation, and are strongly associated with changes in gene expression. [Genome Res] Abstract | Full Article

Determining C-Myb Protein Levels Can Isolate Functional Hematopoietic Stem Cell Subtypes
Scientists generated a novel c-myb allele in mice that allows direct observation of c-Myb protein levels in single cells. Using this reporter line they demonstrate that subtypes of hematopoietic stem cells can be isolated based upon their respective c-Myb protein expression levels. [Stem Cells] Abstract

Medicarpin, a Legume Phytoalexin Sensitizes Myeloid Leukemia Cells to TRAIL-Induced Apoptosis through the Induction of DR5 and Activation of the ROS-JNK-CHOP Pathway
Researchers report that medicarpin, a naturally occurring phytoalexin, sensitizes myeloid leukemia cells to tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. [Cell Death Dis] Full Article

Small Molecule Inhibitor of Glycogen Synthase Kinase 3β 6-Bromoindirubin-3-Oxime Inhibits Hematopoietic Regeneration in Stem Cell Recipient Mice
Scientists investigated the effect of glycogen synthase kinase 3β inhibitor 6-bromoindirubin-3-oxime previously shown to inhibit leukemia cell growth in vitro and animal models on hematopoietic regeneration in recipients of stem cell transplant. [Stem Cells Dev] Abstract

Upregulation of CD11A on Hematopoietic Stem Cells Denotes the Loss of Long-Term Reconstitution Potential
Researchers describe a marker, CD11A, which allows for the enhanced purification of mouse hematopoietic stem cells (HSCs). They show through in vivo transplantations that upregulation of CD11A on HSCs denotes the loss of their long-term reconstitution potential. [Stem Cells Rep] Full Article

Chaetocin Antileukemia Activity against Chronic Myelogenous Leukemia Cells Is Potentiated by Bone Marrow Stromal Factors and Overcomes Innate Imatinib Resistance
Scientists show that chaetocin suppressed viability and colony formation, and induced apoptosis of the murine hematopoietic cell line TonB210 with and without Bcr-Abl expression, and these effects were potentiated by bone marrow stromal cytokines and growth factors. [Oncogenesis] Full Article

CLINICAL RESEARCH

HLA-C Expression Levels Define Permissible Mismatches in Hematopoietic Cell Transplantation
Researchers examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. [Blood] Abstract

Elevated Fluoride Levels and Periostitis in Pediatric Hematopoietic Stem Cell Transplant Recipients Receiving Long-Term Voriconazole
Scientists review fluoride levels, clinical, and laboratory data in five pediatric hematopoietic stem cell transplant recipients on long-term voriconazole therapy, all found to have elevated serum fluoride levels.
[Pediatr Blood Cancer]
Abstract

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REVIEWS
Children as Hematopoietic Cell Donors in Research: When Is it Approvable?
The authors review the issues to be considered while evaluating studies that use hematopoietic stem cells obtained from minor donors and identifies areas where further research is needed. [Bone Marrow Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
 
INDUSTRY NEWS
ERYTECH Announces Granting of New Patent in the United States
ERYTECH, a French biopharmaceutical company that develops ‘tumor starvation’ treatments for acute leukemia and other oncology indications with unmet medical needs, announced the granting of a new patent in the field of asparaginase in the United States. [ERYTECH Pharma] Press Release

The Leukemia & Lymphoma Society Awards Six New Research Grants Focused on Innovative New Ideas
Six academic investigators will receive grants from The Leukemia & Lymphoma Society to support innovative ideas that that have the potential to take research in a new direction and fundamentally impact the future of blood cancer diagnosis and treatment. [The Leukemia & Lymphoma Society] Press Release

IMBRUVICA® (Ibrutinib) Now Approved in Europe for Treatment of Two Blood Cancers
Pharmacyclics, Inc. announced that the European Commission has granted marketing approval for IMBRUVICA® (ibrutinib) throughout the 28 member states of the European Union. [Pharmacyclics, Inc.]
Press Release

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POLICY NEWS
National Institutes of Health (United States)

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)
 
EVENTS
NEW 5th International Conference on Stem Cells and Cancer (ICSCC-2014): Proliferation, Differentiation and Apoptosis
November 8-10, 2014
New Delhi, India

Visit our events page to see a complete list of events in the hematopoiesis community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Research Associate – Mechanisms Underlying Hematopoiesis and Leukemogenesis (University of Wisconsin School of Medicine and Public Health)

Quality Improvement Coordinator – Regenerative Medicine (The University of Texas Health Science Center at Houston)

Postdoctoral Position – Hematopoietic Stem and Progenitor Cell Biology (Lund University)

Postdoctoral Position – Molecular Properties of Leukemic Stem Cells (BC Cancer Agency)

Postdoctoral Position – Regenerative Effects of Some Mutations on Hematopoietic Stem Cells (Istanbul University Institute of Experimental Medicine)

Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

Stem Cell Biology Program Director (Blood Research Institute of BloodCenter of Wisconsin)

Assistant or Associate Professor – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Associate – Cancer, Stem Cells, and Immunity Focusing on Membrane Proteins and Signaling Pathways (UT Southwestern Medical Center)

Postdoctoral Positions – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)


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