Hematopoiesis News Volume 4.28 | Jul 23 2013

Positive Feedback between PU.1 and the Cell Cycle Controls Myeloid Differentiation
Regulatory gene circuits with positive feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Researchers dissected feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. [Science] Abstract

Antagonistic Regulation by the Transcription Factors C/EBPα and MITF Specifies Basophil and Mast Cell Fates
The authors identified a population of granulocyte-macrophage progenitors that were highly enriched in the capacity to differentiate into basophils and mast cells while retaining a limited capacity to differentiate into myeloid cells. They designated these progenitor cells pre-basophil and mast cell progenitors. [Immunity] Abstract | Graphical Abstract

Meta-Analysis of IDH-Mutant Cancers Identifies EBF1 as an Interaction Partner for TET2
Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute myeloid leukemia (AML), low-grade glioma, cholangiocarcinoma (CC) and chondrosarcoma. For AML, low-grade glioma and CC, mutant IDH status is associated with a DNA hypermethylation phenotype, implicating altered epigenome dynamics in the etiology of these cancers. By analyzing sequence motifs surrounding hypermethylated sites across the four cancer types, and using chromatin immunoprecipitation and western blotting, researchers identified the transcription factor EBF1 (early B-cell factor 1) as an interaction partner for TET2, suggesting a sequence-specific mechanism for regulating DNA methylation. [Nat Commun] Full Article

Mouse Extra-Embryonic Arterial Vessels Harbor Precursors Capable of Maturing into Definitive HSCs
Investigators showed that umbilical cord and vitelline arteries, but not veins, contain pre-hematopoietic stem cells (HSCs) capable of maturing into definitive HSCs in the presence of exogenous IL3, although in fewer numbers than the aorta-gonad-mesonephros region, and that pre-HSC activity in vitelline arteries increases with proximity to the embryo proper. [Blood] Abstract

Intestinal Bacteria Modify Lymphoma Incidence and Latency by Affecting Systemic Inflammatory State, Oxidative Stress, and Leukocyte Genotoxicity
Using an ataxia-telangiectasia mouse model, scientists compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress, and systemic leukocyte genotoxicity. [Cancer Res] Abstract | Press Release

Hoxb8 Regulates Expression of MicroRNAs to Control Cell Death and Differentiation
Hoxb8 overexpression immortalizes hematopoietic progenitor cells in a growth-factor-dependent manner and co-operates with interleukin-3 (IL-3) to cause acute myeloid leukemia. To further understand how Hoxb8 contributes to myeloid cell immortalization, researchers generated IL-3-dependent myeloid cells expressing Hoxb8 under the control of an inducible promoter. [Cell Death Differ] Abstract

Fbw7-Dependent Cyclin E Regulation Ensures Terminal Maturation of Bone Marrow Erythroid Cells by Restraining Oxidative Metabolism
The authors examined the physiologic consequences of cyclin E dysregulation in bone marrow erythroid cells during terminal maturation in vivo. [Oncogene] Abstract

CLINICAL RESEARCH

Global Burden of Sickle Cell Anemia in Children under Five, 2010–2050: Modeling Based on Demographics, Excess Mortality, and Interventions
Investigators aimed to estimate trends in the future number of newborns with sickle cell anemia (SCA) and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions. [PLoS Med] Full Article | Press Release

Exome Sequencing Identifies Recurring FLT3 N676K Mutations in Core-Binding Factor Leukemia
In a cohort of 84 de novo AML patients with a CBFB/MYH11 rearrangement and in 36 patients with a RUNX1/RUNX1T1 rearrangement, the FLT3 N676K mutation was identified in five and one patients, respectively (5/84, 6%; 1/36, 3%). [Blood] Abstract

STAT3 Mutations Identified in Human Hematological Neoplasms Induce Myeloid Malignancies in a Mouse Bone Marrow Transplantation Model
Researchers investigated the mutational status of STAT3 in a large series of patients with lymphoid and myeloid diseases. Data indicate that the STAT3Y640F mutation leads to constitutive activation of STAT3, induces malignant hematopoiesis in vivo and may represent a novel therapeutic target in some lymphoid malignancies. [Haematologica] Abstract | Full Article

Biomarkers for Determining the Prognosis in Chronic Myelogenous Leukemia
This review presents the supporting data and discusses how certain clinical characteristics at diagnosis, the depth of early response, the presence of certain kinase domain mutations, and additional molecular changes serve as prognostic factors that may guide individualized treatment decisions for patients with chronic myelogenous leukemia in chronic phase. [J Hematol Oncol] Abstract | Full Article

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

Celgene Will Discontinue Phase III ORIGIN® Trial in Previously Untreated Elderly Patients with B-Cell Chronic Lymphocytic Leukemia
Celgene Corporation announced that after consultation with the U.S. Food and Drug Administration Celgene will discontinue treatment with REVLIMID^® (lenalidomide) in the open-label, phase III ORIGIN® trial, which enrolled 450 patients in over 100 sites in 26 countries. An imbalance was observed in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. [Celgene Corporation]
Press Release

STEMSOFT Announces Release of CIBMTR Upload Interface
STEMSOFT Software Inc. announced the release of the new CIBMTR upload interface, STEMSOFTconnect: REGISTRY. This new solution is designed to allow users to complete, submit and review all AGNIS-defined registry forms locally for seamless upload to the Center for International Blood and Marrow Transplant Research (CIBMTR^®). [STEMSOFT Software Inc.] Press Release

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

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

Postdoctoral Fellow – Cancer Stem Cell Biology (McGill University)

Postdoctoral Position – Hematopoietic Differentiation of Pluripotent Stem Cells (Center for Physiology and Pathophysiology, University of Cologne)

Research Associate (Assistant Professor) – Pediatric Hematology/Oncology (The University of Chicago)

Postdoctoral Research Fellow – Hematology/Pharmacology (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Positions – Stem Cell Biology and Epigenetics (University of Wisconsin-Madison)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

PhD Student Position – Hematopoietic Stem Cells (Katholieke Universiteit Leuven)

Postdoctoral Researcher – Hematopoietic Stem Cells (Albert Einstein College of Medicine)

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

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