Hematopoiesis News Volume 7.24 | Jun 21 2016

TOP STORY

Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits

Researchers employed a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. They used targeted genome editing to demonstrate endogenous enhancer activity across three MPRA functional variants that predominantly affect the transcription of SMIM1, RBM38, and CD164. [Cell] Abstract | Graphical Abstract | Press Release

(Ranked by impact factor of the journal)

Distinct Evolution and Dynamics of Epigenetic and Genetic Heterogeneity in Acute Myeloid Leukemia

Investigators examined epigenetic heterogeneity as assessed by cytosine methylation within defined genomic loci with four CpGs (epialleles), somatic mutations, and transcriptomes of acute myeloid leukemia patient samples at serial time points. [Nat Med] Abstract

Identification of ETV6-RUNX1-Like and DUX4-Rearranged Subtypes in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

Using RNA sequencing, scientists found in-frame fusion genes in 127 cases, including 27 novel fusions. They describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. [Nat Commun] Full Article | Press Release

Aneuploidy Impairs Hematopoietic Stem Cell Fitness and Is Selected Against in Regenerating Tissues In Vivo

Scientists evaluated the fitness of cells with constitutional trisomy or chromosomal instability in vivo using hematopoietic reconstitution experiments. [Genes Dev] Abstract

Loss of Sfrp2 in the Niche Amplifies Stress-Induced Cellular Responses, and Impairs the In Vivo Regeneration of the Hematopoietic Stem Cell Pool

Investigators showed, that co-culture of hematopoietic cells with stromal cells with reduced expression of Sfrp2 increases the number lineage-negative Kit⁺ Sca-1⁺ and progenitor cells in vitro. [Stem Cells] Abstract

Mobilization and Dysfunction of Hematopoietic Stem/Progenitor Cells after Listonella anguillarum Infection in Ayu, Plecoglossus altivelis

The authors established a colony-forming unit culture assay to measure hematopoietic stem/progenitor cells using conditioned medium from peripheral blood mononuclear cells stimulated with phytohemagglutinin. [Sci Rep] Full Article

Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation

The authors showed that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse hematopoietic stem cells (HSC), leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. [Stem Cell Reports] Full Article | Graphical Abstract

Systemic TLR2 Agonist Exposure Regulates Hematopoietic Stem Cells via Cell-Autonomous and Cell-Non-Autonomous Mechanisms

Scientists showed that systemic exposure of mice to a toll-like receptor 2 (TLR2) agonist leads to an expansion of bone marrow and spleen phenotypic hematopoietic stem cells (HSCs) and progenitors, but a loss of HSC self-renewal capacity. [Blood Cancer J] Full Article

CLINICAL RESEARCH

Does FLT3 Mutation Impact Survival after Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Data from the CIBMTR were used to evaluate 511 adult patients with de novo acute myeloid leukemia who underwent hematopoietic stem cell transplantation (HCT) during 2008 through 2011 to determine whether FMS like tyrosine kinase 3 (FLT3) mutations had an impact on HCT outcomes. [Cancer] Abstract

Long-Term Outcomes of HLA-Haploidentical Stem Cell Transplantation Based on an FBCA Conditioning Regimen Compared with Those of HLA-Identical Sibling Stem Cell Transplantation for Hematologic Malignancies

Haploidentical hematopoietic cell transplantation (HCT) based on a fludarabine, busulphan, cyclophosphamide and antilymphocyte globulin (FBCA) conditioning regimen could achieve nearly comparable outcomes to HLA-identical sibling HCT. [Bone Marrow Transplant] Abstract

Treating Hemoglobinopathies Using Gene-Correction Approaches: Promises and Challenges

The authors describe the development and potential application of gene therapy and precision genome-editing approaches for treating sickle cell disease and β-thalassemia. The opportunities and challenges in advancing a curative therapy for hemoglobinopathies are also discussed. [Hum Genet] Abstract

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

Cellectis Announces First Patient Treated in Phase I Trial of UCART19 in Pediatric Acute B Lymphoblastic Leukemia (B-ALL)

Cellectis announced that the first patient has been treated in the Phase I study of UCART19 in pediatric acute B-ALL at the University College of London. [Cellectis] Press Release

ARIAD Initiates Submission of New Drug Application for Brigatinib to the U.S. Food and Drug Administration Ahead of Plan

ARIAD Pharmaceuticals, Inc. announced the initiation of a New Drug Application submission for its investigational anaplastic lymphoma kinase inhibitor, brigatinib, to the U.S. Food and Drug Administration. [ARIAD Pharmaceuticals, Inc.] Press Release

NEW International Society for Experimental Hematology (ISEH) 2016
August 25-28, 2016
San Diego, United States

Visit our events page to see a complete list of events in the hematopoiesis community.

NEW Postdoctoral Fellow – Characterizing and Targeting Cancer Stem Cells (City of Hope)

Technical Sales Representative (STEMCELL Technologies Inc.)

Scientist – Hematology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Hematology and Oncology (Hannover Medical School)

Cytogenetics Laboratory Supervisor (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Hematopoietic Stem Cell Biology (Novartis)

Research Assistants and Associates – Leukemia and Stem Cell Biology (King’s College London)

Postdoctoral Research Associate – Myeloid Leukemia (Upstate Medical University)

Postdoctoral Fellow – Leukemia Lymphoma (Emory University)

Postdoctoral Fellow – Hematopoietic Stem Cell Biology and Blood Disorders (Brigham & Women’s Hospital)

Research Technician – Hematopoietic Stem Cell Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Stem Cell Aging Biology (University of Southern California)

Postdoctoral Fellow – Hematology/Oncology (Boston Children’s Hospital)

Assistant/Associate/Full Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)

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