Volume 5.15 | Apr 22

Hematopoiesis News 5.15 April 22, 2014
Hematopoiesis News
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Researchers Uncover Link between Down Syndrome and Leukemia
Although doctors have long known that people with Down syndrome have a heightened risk of developing acute lymphoblastic leukemia (ALL) during childhood, they haven’t been able to explain why. Now, investigators have uncovered a connection between the two conditions. The researchers tracked the genetic chain of events that links a chromosomal abnormality in Down syndrome to the cellular havoc that occurs in ALL. [Press release from the Dana-Farber Cancer Institute discussing online prepublication in Nature Genetics]
Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

CD166 Regulates Human and Murine Hematopoietic Stem Cells and the Hematopoietic Niche
Scientists demonstrated that CD166 is a functional hematopoietic stem cell marker that identifies both murine and human long-term repopulating cells. Both murine LSKCD48-CD166+CD150+ and LSKCD48-CD166+CD150+CD9+ cells as well as human Lin-CD34+CD38-CD49f+CD166+ cells sustained significantly higher levels of chimerism in primary and secondary recipients than CD166- cells. [Blood] Abstract

Depletion of Sf3b1 Impairs Proliferative Capacity of Hematopoietic Stem Cells but Is Not Sufficient to Induce Myelodysplasia
Investigators analyzed the function of pre-mRNA splicing factor Sf3b1 in hematopoiesis. Sf3b1+/- mice maintained almost normal hematopoiesis and did not develop hematological malignancies during a long observation period. [Blood] Abstract

EDAG Positively Regulates Erythroid Differentiation and Modifies GATA1 Acetylation through Recruiting p300
Researchers found that EDAG is highly expressed in CMPs and MEPs and upregulated during the erythroid differentiation of CD34+ cells following erythropoietin treatment. [Stem Cells] Abstract

Evi1 Defines Leukemia-Initiating Capacity and Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia
Ecotropic viral integration site 1 (Evi1)-internal ribosomal entry site-green fluorescent protein allele models of chronic myeloid leukemia in chronic phase (CML-CP), by retroviral overexpression of BCR-ABL and by crossing BCR-ABL transgenic mice, revealed that Evi1 is predominantly enriched in the stem cell fraction and associated with an enhanced proliferative as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit resistance to tyrosine kinase inhibitors. [Oncogene] Full Article

Targeted shRNA Screening Identified Critical Roles of Pleckstrin-2 in Erythropoiesis
Using a mouse fetal liver erythroblast culture system and a targeted shRNA functional screening strategy, investigators identified a critical role of pleckstrin-2 in actin dynamics and protection of early stage terminal erythroblasts from oxidative damage. [Haematologica] Abstract | Full Article

IL-3 and CSF-1 Interact to Promote Generation of CD11c+ IL-10-Producing Macrophages
Researchers uncovered an instructive role of CSF-1 in interleukin-3 (IL-3)-mediated hematopoiesis. CSF-1 significantly promoted IL-3-driven CD11c+ cell expansion and dampened basophil and mast cell generation from C57BL/6 bone marrow. [PLoS One] Full Article

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions
Investigators analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. Acute myeloid leukemia patients’ blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. [PLoS One] Full Article


Validation and Refinement of the Disease Risk Index for Allogeneic Stem Cell Transplantation: A Study from the CIBMTR
Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is predominantly influenced by disease type and status, it is essential to be able to stratify patients undergoing HCT by disease risk. The Disease Risk Index was developed for this purpose. Investigators analyzed 13,131 patients reported to the CIBMTR who underwent HCT between. [Blood] Abstract

Outcomes of Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Disease with Myeloablative Conditioning and Intermediate-Dose of Rabbit Anti-Thymocyte Globulin
Investigators postulated that an intermediate dose of rabbit anti-thymocyte (r-ATG) globulin would be effective in preventing both rejection and graft versus host disease. Fifteen patients, median age 5 (range 1.5-18) years, underwent matched sibling donor hematopoietic stem cell transplantation using busulfan, cyclophosphamide and r-ATG. [Pediatr Blood Cancer] Abstract

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Androgen Receptor Differential Roles in Stem/Progenitor Cells Including Prostate, Embryonic, Stromal, and Hematopoietic Lineages
Investigators summarized the androgen receptor (AR) effects on the behavior of stem/progenitor (S/P) cells, including self-renewal, proliferation, apoptosis and differentiation in normal S/P cells, as well as proliferation, invasion and self-renewal in prostate cancer S/P cells. AR plays a protective role in the oxidative stress-induced apoptosis in embryonic stem cells. AR promotes the proliferation of hematopoietic S/P cells and stimulates hematopoietic lineage differentiation. [Stem Cells] Abstract | Full Article

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

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Mast Therapeutics Announces New Data Supporting MST-188 in Sickle Cell Disease
In an ex vivo study, MST-188 reduced the mean erythrocyte sedimentation rate (ESR) by 50% relative to control in blood collected from individuals with sickle cell disease. ESR, a common laboratory test and measure of inflammation, describes the rate at which red blood cells travel through anti-coagulated blood. [Press release from Mast Therapeutics, Inc. discussing research presented at the 8th Annual Sickle Cell Disease Research & Educational Symposium, Miami] Press Release

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GSK and Genmab Receive FDA Approval for Arzerra® (Ofatumumab) as First-Line Treatment in Combination with Chlorambucil for Patients with Chronic Lymphocytic Leukemia (CLL) for Whom Fludarabine-Based Therapy Is Considered Inappropriate
GlaxoSmithKline plc and Genmab A/S announced that the U.S. Food and Drug Administration (FDA) has approved a Supplemental Biologic License Application for the use of Arzerra® (ofatumumab), a CD20-directed cytolytic monoclonal antibody, in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. [GlaxoSmithKline plc]
Press Release

First Volunteers to Receive Blood Cultured from Stem Cells in 2016
Red blood cells cultured in a laboratory will be trialed in human volunteers for the first time within the next three years, as part of a long-term research program funded by the Wellcome Trust. The £5 million Strategic Award was granted to a consortium led by the Scottish National Blood Transfusion Service, and will follow on from previous research that proved that red blood cells could be generated from stem cells. [Wellcome Trust]
Press Release
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)
NEW American Society of Hematology (ASH) Meeting on Lymphoma Biology 2014
August 10-13, 2014
Colorado Springs, United States

Visit our events page to see a complete list of events in the hematopoiesis research community.
NEW Postdoctoral Fellowship – Hematology, Immunology, Cancer Therapeutics (Nationwide Children’s Hospital)

Postdoctoral Position – Development of Novel Treatment for Mixed Lineage Leukemia (Oslo University Hospital)

Postdoctoral Researcher – Regulation of Lymphoid Development (Lund University)

MSc & PhD Positions – Cell Biology, Neurobiology, Neuroimmunology, Cancer Biology, Computational Biology (Hanyang University)

Research Associate – Hematology/Oncology (University of Chicago)

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

Postdoctoral Position – Immunotherapies for Cancer Based on Genetic Engineered T Lymphocytes and/or Hematopoietic Stem Cells (Roswell Park Cancer Institute)

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

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

Postdoctoral Position – Human Stem Cell Biology and Hematopoiesis (Johns Hopkins University School of Medicine)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

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

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