Volume 4.16 | Apr 30

Hematopoiesis News 4.16 April 30, 2013
Hematopoiesis News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Quantitative Imaging of Hematopoietic Stem and Progenitor Cell Localization and Hypoxic Status in the Bone Marrow Microenvironment
Researchers employed a powerful imaging cytometry platform to perform a comprehensive quantitative analysis of hematopoietic stem and progenitor cell (HSPC) distribution in bone marrow cavities of femoral bones. They found that HSPCs preferentially localize in endosteal zones, where most closely interact with sinusoidal and non-sinusoidal bone marrow microvessels, which form a distinctive circulatory system. [Nat Cell Biol] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

CD40 Ligation Reverses T Cell Tolerance in Acute Myeloid Leukemia
A murine acute myeloid leukemia (AML) model was used to investigate antigen-specific T cell responses against AML cells inoculated i.v. versus s.c. [J Clin Invest] Full Article

Lineage Inappropriate PAX5 Expression in t(8;21) Acute Myeloid Leukemia Requires Signaling Mediated Abrogation of Polycomb Repression
To understand the molecular mechanism of PAX5 deregulation, researchers examined its chromatin structure and regulation in t(8;21) acute myeloid leukemia cells, non-t(8;21) myeloid precursor control cells and in pre-B cells. [Blood] Abstract

Targeting Oncogene Expression to Endothelial Cells Induces Proliferation of the Myelo-Erythroid Lineage by Repressing the Notch Pathway
Investigators used a zebrafish genetic model to induce the expression of oncogenic RAS in endothelial cells, including the hemogenic endothelium of the dorsal aorta that generates hematopoietic cells, and observed the development of a myelo-erythroid proliferative disorder. [Leukemia] Abstract

Dynamics of Thymus Organogenesis and Colonization in Early Human Development
Researchers demonstrated, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. They defined the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. [Development] Full Article

Rac1 Signaling Protects Monocytic AML Cells Expressing the MLL-AF9 Oncogene from Caspase-Mediated Apoptotic Death
The authors investigated the relevance of signaling mechanisms regulated by the Ras-homologous GTPase Rac1 for survival of acute myeloid leukemia (AML) cells harboring the MLL-AF9 oncogene due to t(9;11)(p21;q23) translocation. [Apoptosis] Abstract

Up-Regulated Expression of CXCL12 in Human Spleens with Extramedullary Hematopoiesis
Scientists aimed to determine the expression of CXCL12 in human spleens with extramedullary hematopoiesis for clarifying the association of splenic hematopoietic stem cells with CXCL12, which has been demonstrated to be a marker of bone marrow niches. [Pathology] Abstract

Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
Researchers describe a method of isolating and culturing human bone marrow stromal stem/progenitor cells as nonadherent mesenchymal spheres. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded hematopoietic stem cells were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. [Cell Rep] Abstract | Full ArticleGraphical Abstract

Effect of Intravenous Coadministration of Human Stroma Cell Lines on Engraftment of Long-Term Repopulating Clonal Myelodysplastic Syndrome Cells in Immunodeficient Mice
Investigators used intravenous coadministration of the human marrow stroma cell line HS27a with CD34+ myelodysplastic syndrome (MDS) cells in Nod.cg-Prkdcscid Il2rgtm1wjll mice to provide signals that would facilitate engraftment. Hematopoietic cells from 24 MDS patients were transplanted. [Blood Cancer J]
Full Article

CLINICAL RESEARCH

Early Responses Predicts for Better Outcomes in Patients with Newly Diagnosed CML: Results with Four TKI Modalities
Early responses to tyrosine kinase inhibitors (TKI) in CML-CP are associated with improved outcome. The authors analyzed the impact of such response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. [Blood] Abstract

Old and New Prognostic Factors in Acute Myeloid Leukemia with Deranged Core-Binding Factor Beta
Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50-70% of patients cured using contemporary treatments. Researchers analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. [Am J Hematol] Abstract

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REVIEWS

Signaling Pathways that Control Vertebrate Hematopoietic Stem Cell Specification
The authors review current knowledge of the intraembryonic signals required for the specification of hematopoietic stem cells in vertebrates. [Nat Rev Immunol] Abstract

MicroRNAs in Hematological Malignancies
Scientists provide an overview of the role and potential clinical utility for microRNAs in hematological malignancies and their function in normal hematopoiesis. [Blood Rev] Abstract

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

SCIENCE NEWS
Majority of Children Readmitted to Hospital following Transplant
Nearly two-thirds of children receiving stem cell transplants returned to the hospital within six months for treatment of unexplained fevers, infections or other problems, according to a study. Children who received donor cells were twice as likely to be readmitted as children who received their own stem cells. [Press release from Dana-Farber Cancer Institute discussing research presented at the 26th Annual Meeting of the American Society of Pediatric Hematology Oncology, Miami] Press Release

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INDUSTRY NEWS

Team PhRMA Raises $100,000 for Leukemia/Lymphoma Research
The Pharmaceutical Research and Manufacturers of America (PhRMA) has raised more than $100,000 to establish a new grant for blood cancer research. [Pharmaceutical Research and Manufacturers of America] Press Release

More Than 240 Innovative Medicines in Development for Leukemia, Lymphoma and Other Blood Cancers
America’s biopharmaceutical research companies are developing 241 medicines for blood cancers – leukemia, lymphoma and multiple myeloma, according to a new report and overview released by the Pharmaceutical Research and Manufacturers of America. [Pharmaceutical Research and Manufacturers of America] Press Release

MorphoSys Initiates Phase II Study of Anti-CD19 Antibody MOR208 in B-Cell Acute Lymphoblastic Leukemia
MorphoSys AG announced that it has dosed the first patient in a Phase II clinical trial of MOR208 in B-cell acute lymphoblastic leukemia. MOR208 is a potent monoclonal Fc optimized anti-CD19 antibody to which MorphoSys gained worldwide access via an exclusive license and collaboration agreement with Xencor in 2010. [MorphoSys AG] Press Release

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 ISEH Society for Hematology and Stem Cells: Combinatorial Transcriptional Control of Blood Stem and Progenitor Cells
June 6, 10:00AM (ET in US)
Webinar

Visit our events page to see a complete list of events in the hematopoietic community.
JOB OPPORTUNITIES
NEW Postdoctoral Position (Inselspital Bern, University Hospital Bern)

NEW Postdoctoral Fellow – Myeloproliferative Neoplasms (Mount Sinai Medical Center)

NEW Postdoctoral Positions – Stem Cell Biology and Aging (Children’s Hospital Oakland Research Institute)

Cord Blood Laboratory Manager (Puget Sound Blood Center)

Postdoctoral Positions (Cancer Science Institute of Singapore)

Postdoctoral Position – Hematopoietic Stem Cell Biology (Institut Pasteur, Labex Revive)

Postdoctoral Scholarship – Leukemia Stem Cell Biology (Lund University – Faculty of Medicine)

Studentship – Novel Mechanisms in Blood Cancers Drug-Resistance (University of East Anglia)


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