Hematopoiesis News Volume 5.13 | Apr 8 2014

A Single Oncogenic Enhancer Rearrangement Causes Concomitant EVI1 and GATA2 Deregulation in Leukemia
AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, scientists demonstrated that both 3q rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. [Cell] Abstract | Graphical Abstract

Analysis of the DNA Methylome and Transcriptome in Granulopoiesis Reveal Timed Changes and Dynamic Enhancer Methylation
Scientists characterized changes in DNA methylation and gene expression during granulopoiesis using four distinct cell populations ranging from the oligopotent common myeloid progenitor stage to terminally differentiated neutrophils. [Blood] Abstract | Press Release

JAK2V617F-Homozygosity Drives a Phenotypic Switch between Myeloproliferative Neoplasms in a Murine Model, but Is Insufficient to Sustain Clonal Expansion
Researchers provided direct genetic evidence and demonstrated that homozygosity for human JAK2V617F in knock-in mice results in a striking phenotypic switch from an essential thrombocythemia-like to polycythemia vera-like phenotype. The resultant erythrocytosis is driven by increased numbers of early erythroid progenitors and enhanced erythroblast proliferation whereas reduced platelet numbers are associated with impaired platelet survival. [Blood] Abstract

CD44 Standard and CD44v10 Isoform Expression on Leukemia Cells Distinctly Influences Niche Embedding of Hematopoietic Stem Cells
A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore, investigators explored whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. [J Hematol Oncol]
Full Article

Stem and Progenitor Cell Subsets Are Affected by JAK2 Signaling and Can Be Monitored by Flow Cytometry
Investigators analyzed hematopoietic stem cell subsets with a series of stem cell markers in JAK2V617F transgenic mice, where the mutation is sufficient to cause myeloproliferative neoplasia with lymphocyte deficiency. [PLoS One] Full Article

Overexpression of miR-125a in Myelodysplastic Syndrome CD34⁺ Cells Modulates NF-κB Activation and Enhances Erythroid Differentiation Arrest
The authors studied the role of miR-125a/miR-125b in myelodysplastic syndromes (MDS) and their relationship with toll-like receptor (TLR) signaling and hematopoietic differentiation. Their results indicate that miR-125a is significantly overexpressed in MDS patients and correlates negatively with patient survival. [PLoS One]
Full Article

CLINICAL RESEARCH

The Prognostic Impact of Minimal Residual Disease in Patients with Chronic Lymphocytic Leukemia Requiring First-Line Therapy
Researchers retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any frontline therapy in the context of a detailed prognostic evaluation, including IGHV, TP53, NOTCH1 and SF3B1 mutations. [Haematologica] Abstract | Full Article

Extramedullary Relapse of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Different Characteristics between Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia
In order to investigate the incidence, risk factor and clinical outcome of extramedullary relapse for acute myeloid leukemia and acute lymphoblastic leukemia, scientists performed a retrospective analysis on 362 patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation. [Biol Blood Marrow Transplant] Abstract

Thioredoxin-Interacting Protein, Hematopoietic Stem Cells, and Hematopoiesis
Thioredoxin-interacting protein (TXNIP) is expressed in hematopoietic stem cells (HSCs), and its expression decreases as HSCs differentiate into precursor cells. However, this reduction in expression does not sufficiently explain the function of TXNIP in hematopoietic cells under oxidative stress conditions. The authors review how reactive oxygen species can regulate hematopoiesis by focusing on the function of TXNIP in hematopoietic cells under oxidative stress conditions. [Curr Opin Hematol] Abstract

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Ambit Announces Initiation of Phase II Cohort in MD Anderson Sponsored Study of Quizartinib in AML and High Risk MDS
Ambit Biosciences announced the initiation of the Phase II cohort of the MD Anderson Cancer Center-sponsored Phase I/II study of quizartinib in combination with either 5-azacitidine or low dose cytarabine for previously untreated FLT3-ITD positive acute myeloid leukemia (AML) patients age 60 or older, or FLT3-ITD positive AML patients 18 years of age or older in first relapse. [Ambit Biosciences Corporation] Press Release

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NEW MSc & PhD Positions – Cell Biology, Neurobiology, Neuroimmunology, Cancer Biology, Computational Biology (Hanyang University)

Research Associate – Hematology/Oncology (University of Chicago)

Postdoctoral Fellow – Hematopoietic Stem Cell and Leukemia Research (City of Hope)

Postdoctoral Position – Immunotherapies for Cancer Based on Genetic Engineered T Lymphocytes and/or Hematopoietic Stem Cells (Roswell Park Cancer Institute)

Postdoctoral Fellow – Mammalian Hematopoietic and Erythroid Development (The Icahn School of Medicine at Mount Sinai)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Position – Human Stem Cell Biology and Hematopoiesis (Johns Hopkins University School of Medicine)

Postdoctoral Position – Genes that Regulate Hematopoietic Stem Cells (University of Chicago)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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