Volume 4.19 | May 21

Hematopoiesis News 4.19 May 21, 2013
Hematopoiesis News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Natural Killer Cells Activate Hematopoiesis
Infections can trigger hematopoiesis at sites outside the bone marrow – in the liver, the spleen or the skin. Researchers showed that a specific type of immune cell facilitates such “extra medullary” formation of blood cells. [Press release from Ludwig-Maximilians-Universität München discussing online prepublication in Cell Host & Microbe] Press Release | Abstract | Graphical Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

viSNE Enables Visualization of High Dimensional Single-Cell Data and Reveals Phenotypic Heterogeneity of Leukemia
Investigators presented viSNE, a tool that allows one to map high-dimensional cytometry data onto two dimensions, yet conserve the high-dimensional structure of the data. They integrated mass cytometry with viSNE to map healthy and cancerous bone marrow samples. They also use viSNE and mass cytometry to compare leukemia diagnosis and relapse samples, and to identify a rare leukemia population reminiscent of minimal residual disease. [Nat Biotechnol] Abstract

CXCR4 Downregulation of let-7a Drives Chemoresistance in Acute Myeloid Leukemia
Scientists examined the role of microRNAs in targeting the stromal-derived factor 1α/CXCR4 axis to overcome chemoresistance of acute myeloid leukemia cells. [J Clin Invest] Full Article

NrasG12D/+ Promotes Leukemogenesis by Aberrantly Regulating Hematopoietic Stem Cell Functions
Researchers showed that hematopoietic stem cells expressing NrasG12D/+ serve as myeloproliferative neoplasm initiating cells. [Blood] Abstract

Human iPS Cell-Derived Hematopoietic Progenitor Cells Induce T-Cell Anergy in In Vitro Generated Alloreactive CD8+ T-Cells
The authors characterized human induced pluripotent stem (iPS) cell-derived CD34+ hematopoietic progenitor cells (HPCs). The data indicate for the first time that HPCs induce T-cell anergy, a unique characteristic of iPS cell-derived cells that confers immunological advantage for allogenic transplantation. [Blood] Abstract

Kit Receptor Gain-of-Function in Hematopoiesis Enhances Stem Cell Self-Renewal and Promotes Progenitor Cell Expansion
Researchers demonstrated that signaling from the KitV558Δ;T669I/+ receptor has important consequences in hematopoiesis enhancing hematopoietic stem cell self-renewal and resulting in increased erythropoiesis. [Stem Cells] Abstract | Full Article

Deregulation of Apoptotic Factors Bcl-xL and Bax Confers Apoptotic Resistance to Myeloid- Derived Suppressive Cells and Contributes to Their Persistence in Tumors
Investigators demonstrated that tumor-induced myeloid-derived suppressive cells exhibit significantly decreased spontaneous apoptosis as compared to myeloid cells with the same phenotype from tumor-free mice. [J Biol Chem] Abstract | Full Article

Stat and Interferon Genes Identified by Network Analysis Differentially Regulate Primitive and Definitive Erythropoiesis
Hematopoietic ontogeny is characterized by overlapping waves of primitive, fetal definitive, and adult definitive erythroid lineages. Researchers aimed to identify differences in the transcriptional control of these distinct erythroid cell maturation pathways by inferring and analyzing gene-interaction networks from lineage-specific expression datasets. [BMC Syst Biol] Abstract | Full Article

Radiation Dose-Response of Glycophorin A Somatic Mutation in Erythrocytes Associated with Gene Polymorphisms of p53 Binding Protein 1
It is hypothesized that persistent glycophorin A (GPA) mutations in erythrocytes of atomic-bomb survivors are derived from those in long-lived hematopoietic stem cell (HSC) populations, and that individual genetic backgrounds, specifically related to DNA double-strand break repair, contribute to individual differences in HSC mutability following radiation exposure. Researchers examined the relationship between radiation exposure, GPA mutant fraction in erythrocytes, and single nucleotide polymorphisms of the key gene involved in DNA double-strand break repair, p53 binding protein 1. [Mutat Res] Abstract

CLINICAL RESEARCH

Duration of First Remission, Hematopoietic Cell Transplantation-Specific Comorbidity Index and Patient Age Predict Survival of Patients with AML Transplanted in Second CR
Allo-SCT is potentially curative for patients with AML. Patients transplanted in CR2 tend to experience inferior survival compared with those in CR1. Researchers retrospectively investigated the impact of pretransplant variables on the outcome of patients transplanted with AML in CR2. [Bone Marrow Transplant] Abstract

Impact of Polymorphisms in Drug Pathway Genes on Disease-Free Survival in Adults with Acute Myeloid Leukemia
At the authors’ institution, cytarabine, etoposide and busulfan are used in first or second remission patients treated with a two-step approach to autologous stem cell transplantation. They tested the hypothesis that polymorphisms in the pharmacokinetic and pharmacodynamic pathway genes of these drugs are associated with disease-free survival in acute myeloid leukemia patients. [J Hum Genet] Abstract

A New System for High-Throughput Cell Isolation Directly from Whole Blood

REVIEWS
Targeting Self-Renewal Pathways in Myeloid Malignancies
Key activators/regulators of hematopoietic stem cell (HSC) self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behavior. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. The authors focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies. [Cell Commun Signal] Abstract | Full Article

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

World Stem Cells & Regenerative Medicine Congress 2013 | May 21-23 | London, UK
SCIENCE NEWS
Gilead Announces Response Data from Phase II Study of Idelalisib for Previously Untreated Chronic Lymphocytic Leukemia
Gilead Sciences, Inc. announced results from a Phase II study evaluating idelalisib (formerly GS-1101), an investigational, targeted, oral inhibitor of PI3K delta, in combination with rituximab for older patients with treatment-naïve chronic lymphocytic leukemia. [Press release from Gilead Sciences, Inc. discussing research presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago]
Press Release

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INDUSTRY NEWS

NeoStem Announces Geographic Expansion of Intellectual Property Coverage of Cardiovascular Asset AMR-001
NeoStem, Inc. announced the geographic expansion of intellectual property protection around its lead product candidate, AMR-001, with the notice of patent grant in Malaysia and notice of recommendation for patent allowance in the Philippines. These patents are in the family of U.S. patent number 7,794,705 titled “Compositions and Methods of Vascular Injury Repair” and protect a chemotactic stem cell product enriched for CD34+ cells that treats injury from acute myocardial infarction. [NeoStem, Inc.] Press Release

Sanofi Reports Positive Topline Results from Pivotal Phase III JAKARTA Study for JAK2 Inhibitor in Myelofibrosis
Sanofi announced that the pivotal study, JAKARTA, examining the selective JAK2 inhibitor SAR302503 for myelofibrosis, met its primary endpoint in both dose groups. The primary endpoint assessed the proportion of patients achieving >35% reduction of spleen volume. [Sanofi] Press Release

Seattle Genetics Announces ADCETRIS® (Brentuximab Vedotin) Supplemental BLA Accepted for Filing by the FDA
Seattle Genetics, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplement to the Biologics License Application (sBLA) supporting the use of ADCETRIS for retreatment and extended duration beyond 16 cycles of therapy in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. [Seattle Genetics, Inc.] Press Release

NIH Saves Lives: Fred Hutchinson Cancer Research Center Calls on Congress to Restore Full NIH Funding
Fred Hutchinson Cancer Research Center called on Congress to support restoring full funding to the National Institutes of Health (NIH), which supports pioneering research that saves lives. Funding was recently cut due to sequestration. [Fred Hutchinson Cancer Research Center] 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 Cold Spring Harbor Laboratory: Stem Cell Biology
September 24-28, 2013
Cold Spring Harbor, United States

Visit our events page to see a complete list of events in the hematopoietic community.
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Hematopoietic and Malignant Stem Cells (Istanbul University Institute of Experimental Medicine)

Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Position (Inselspital Bern, University Hospital Bern)

Postdoctoral Fellow – Myeloproliferative Neoplasms (Mount Sinai Medical Center)

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

Postdoctoral Positions (Cancer Science Institute of Singapore)

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


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