Hematopoiesis News Volume 4.19 | May 21 2013

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

Nras^G12D/+ Promotes Leukemogenesis by Aberrantly Regulating Hematopoietic Stem Cell Functions
Researchers showed that hematopoietic stem cells expressing Nras^G12D/+ 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 Kit^{V558Δ;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

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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

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)

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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