Volume 5.05 | Feb 11

Hematopoiesis News 5.05 February 11, 2014
Hematopoiesis News
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Normal Enzyme Aids a Mutant One to Fuel Blood Cancer’s Growth
Researchers reported that a normal enzyme called SYK pairs with FLT3, the most commonly mutated enzyme found in acute myelogenous leukemia (AML), to promote progression of the disease. This molecular partnership also promotes AML cells’ resistance to treatment with FLT3-blocking drugs, potentially explaining the relatively poor showing of FLT3 inhibitors in multiple clinical studies. [Press release from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center discussing online prepublication in Cancer Cell] Press Release | Abstract
Learn more about the new smartphone app for human blood cell frequencies
PUBLICATIONS (Ranked by impact factor of the journal)

Identification of Functional Cooperative Mutations of SETD2 in Human Acute Leukemia
Researchers provided compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development. [Nat Genet]
Abstract | Press Release

Epigenetic Regulation of GATA2 and Its Impact in Normal Karyotype Acute Myeloid Leukemia
Using RNAseq researchers report that GATA2 is either mutated with functional consequence, or expressed at low levels in the majority of normal karyotype acute myeloid leukemia. [Leukemia] Abstract

Chimeric Antigen Receptors against CD33/CD123 Antigens Efficiently Target Primary Acute Myeloid Leukemia Cells In Vivo
Researchers describe the in vivo efficacy and safety of using cytokine-induced-killer cells genetically modified to express anti-CD33 or anti-CD123 chimeric antigen receptor to target acute myeloid leukemia. [Leukemia] Abstract

A Non-Canonical Function of Telomerase RNA in the Regulation of Developmental Myelopoiesis in Zebrafish
Investigators showed that genetic depletion of the telomerase RNA component in the zebrafish results in impaired myelopoiesis, despite normal development of hematopoietic stem cells. [Nat Commun] Abstract

B-myb Is an Essential Regulator of Hematopoietic Stem Cell and Myeloid Progenitor Cell Development
Researchers showed that conditional inactivation of B-myb in vivo results in depletion of the hematopoietic stem cell pool, leading to profound reductions in mature lymphoid, erythroid, and myeloid cells. [Proc Natl Acad Sci USA] Abstract | Full Article

DNMT3A Arg882 Mutation Drives Chronic Myelomonocytic Leukemia through Disturbing Gene Expression/DNA Methylation in Hematopoietic Cells
The authors addressed the transformation ability of the DNA methyltransferase 3A (DNMT3A)-Arg882His (R882H) mutant by using a retroviral transduction and bone marrow transplantation approach and found that the mutant gene can induce aberrant proliferation of hematopoietic stem/progenitor cells. [Proc Natl Acad Sci USA] Abstract

Regulation of Trib2 by an E2F1-C/EBPalpha Feedback Loop in AML Cell Proliferation
Researchers showed that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPalpha and Trib2 in acute myeloid leukemia (AML) cell proliferation and survival. [Blood] Abstract

Stage-Specific Roles for Cxcr4 Signaling in Murine Hematopoietic Stem/Progenitor Cells in the Process of Bone Marrow Repopulation
Investigators concluded that timely regulation of C-X-C chemokine receptor type 4 (Cxcr4)/CXCR4 signaling is key in providing donor hematopoietic stem/progenitor cells (HSPCs) with enhanced repopulation potential following transplantation, whilst preserving the ability to release HSPC progeny into peripheral blood for improved transplantation outcomes. [Stem Cells] Abstract


The Addition of Sirolimus to Tacrolimus/Methotrexate GvHD Prophylaxis in Children with ALL: A Phase III COG/PBMTC Trial
Researchers tested whether addition of sirolimus to GvHD prophylaxis of children undergoing transplantation for ALL would decrease acute GvHD and relapse, thus improving survival. [Blood] Abstract

HLA-Haploidentical Hematopoietic SCT from Collateral Related Donors without In Vitro T-Cell Depletion for Hematological Malignancies
The authors compared clinical outcomes of patients with hematological malignancies, who underwent haploidentical hematopoietic SCT from collateral related donors (n=30) and immediate related donors (n=120). [Bone Marrow Transplant] Abstract

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Emerging Roles of Hematopoietic Cells in the Pathobiology of Diabetic Complications
There is emerging evidence that diabetes compromises the function of the bone marrow (BM), producing a stem cell niche-dependent defect in hematopoietic stem cell mobilization. Furthermore, dysfunctional BM-derived hematopoietic cells contribute to diabetic complications. [Trends Endocrinol Metab] Abstract

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REGiMMUNE Begins Enrollment for Phase II Clinical Trial for Graft versus Host Disease
REGiMMUNE Corporation announced that it has begun a Phase II study of its proprietary compound RGI-2001 for GvHD associated with hematopoietic stem cell transplantation. [REGiMMUNE Co., Ltd.] Press Release

Actinium Engages Goodwin Biotechnology to Supply Iomab™-B for Its Phase III Clinical Study
Actinium Pharmaceuticals, Inc. announced that the company entered into a manufacturing supply agreement with Goodwin Biotechnology, Inc. According to the agreement, Goodwin will oversee the current Good Manufacturing Practices production of a monoclonal antibody anticipated to be used in an upcoming Phase III clinical trial of Iomab™-B. Iomab™-B will be used in preparing patients for hematopoietic stem cell transplant. [Actinium Pharmaceuticals, Inc.] Press Release

Data on More than 10,000 Cancer Genomes Released by the International Cancer Genome Consortium
The International Cancer Genome Consortium announced that it has made available to the scientific community data from more than 10,000 cancer genomes. The data can be used by cancer researchers around the world to better understand the genomic basis of cancer, accelerate cancer research and aid in the development of more targeted treatments. [International Cancer Genome Consortium] Press Release

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Judges Side with FDA on Stem Cells
The D.C. Circuit Court of Appeals ruled that culturing a patient’s stem cells for therapeutic use falls under the aegis of the US Food and Drug Administration (FDA). FDA has said therapeutic stem cells should be regulated as drugs. [TheScientist] Editorial | Court Ruling

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 Clinical Translation of Stem Cells 2014
April 21-22, 2014
Palm Desert, United States

NEW 19th Congress of the European Hematology Association (EHA)
June 12-15, 2014
Milan, Italy

Visit our events page to see a complete list of events in the hematopoiesis research community.
NEW Postdoctoral Fellow – Erythropoiesis and Iron Metabolism (University of Wisconsin – Madison)

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

Postdoctoral Positions – New Models of Hematopoiesis and Hematopoietic Disorders (Mount Sinai Medical Center)

Assistant Professorship – Hematopoietic Stem Cells and Microenvironment (University of Zurich)

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

Postdoctoral Position – Hematopoietic Stem Cell Physiology and Bone Marrow Failure (University of Michigan)

Research Associate – Normal & Leukemic Stem Cells (King’s College London)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Scientific Affairs Coordinator (American Society of Hematology)

Postdoctoral Position – Erythroid and Myeloid Differentiation of Hematopoietic Stem Cells (Imagine Institute)

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