Hematopoiesis News Volume 5.38 | Oct 7 2014

SIRT1 Activation by a c-MYC Oncogenic Network Promotes the Maintenance and Drug Resistance of Human FLT3-ITD Acute Myeloid Leukemia Stem Cells
Investigators show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD acute myeloid leukemia stem cells. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. [Cell Stem Cell] Full Article | Graphical Abstract

TNF-Mediated Inflammation Represses GATA1 and Activates p38 MAP Kinase in RPS19 Deficient Hematopoietic Progenitors
Scientists found that RPS19 deficiency in hematopoietic progenitor cells leads to decreased GATA1 expression in the erythroid progenitor population and p53-dependent upregulation of TNF-α in non-erythroid cells. [Blood] Abstract

Growth Hormone Receptor Signaling Is Dispensable for HSC Function and Aging
Repeat challenge with 5-fluorouracil showed that growth hormone receptor (Ghr) was dispensable for hematopoietic stem cell (HSC) activation and homeostatic recovery in vivo and, following challenge, Ghr-deficient HSCs functioned normally through serial transplantation. [Blood] Abstract

Identification of a Dynamic Core Transcriptional Network in t(8;21) AML that Regulates Differentiation Block and Self-Renewal
Researchers used digital footprinting and chromatin immunoprecipitation sequencing to identify the core RUNX1/ETO-responsive transcriptional network of t(8;21) cells. They show that the transcriptional program underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind to identical DNA sites in a mutually exclusive fashion. [Cell Rep]
Full Article | Graphical Abstract

The Orphan Nuclear Receptor NR4A1 Specifies a Distinct Subpopulation of Quiescent Myeloid-Biased Long-Term HSCs
Investigators show that NR4A1 is most highly expressed in a subset of Lin^–Sca-1⁺c-Kit⁺ CD48^–CD150⁺ long-term hematopoietic stem cells (HSCs), and its expression is tightly associated with HSC quiescence. They also demonstrate that NR4A1 expression in HSCs is induced by PGE₂, a known enhancer of stem cell engraftment potential. [Stem Cells] Abstract

Simultaneous Deletion of p21^Cip1/Waf1 and Caspase-3 Accelerates Proliferation and Partially Rescues the Differentiation Defects of Caspase-3 Deficient Hematopoietic Stem Cells
Depletion of both Caspase-3 and p21^Cip1/Waf1 resulted in an more pronounced increase in the frequency of hematopoietic stem and progenitor cells. [PLoS One] Full Article

CLINICAL RESEARCH

CD45RA Depletion in HLA-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation for Primary Combined Immunodeficiency: A Preliminary Study
Five consecutive patients with combined immunodeficiencies and chronic viral infections underwent an allogeneic, HLA-mismatched hematopoietic stem cell transplantation. Investigators analyzed whether the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens. [J Allergy Clin Immunol] Abstract

Impact of Donor Age on Outcome after Allogeneic Hematopoietic Cell Transplantation
The authors studied the impact of donor age on the tempo of hematopoietic engraftment and donor chimerism, acute and chronic graft-vs.-host disease, and non-relapse mortality among 1,174 consecutive patients undergoing myeloablative and 367 patients undergoing non-myeloablative hematopoietic cell transplantation from HLA-matched related or unrelated donors with G-CSF-mobilized peripheral blood mononuclear cell allografts. [Biol Blood Marrow Transplant] Abstract

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Aptose Biosciences Joins the Leukemia & Lymphoma Society’s Groundbreaking Beat AML Research Initiative with Oregon Health & Science University
Aptose Biosciences Inc. announced that it has joined the Beat AML collaboration. Beat AML is a groundbreaking research initiative that includes industry and academic collaborators led by top scientists within the Knight Cancer Institute in collaboration with The Leukemia & Lymphoma Society. [Aptose Biosciences Inc.]
Press Release

Sunesis Announces Results from Pivotal Phase III VALOR Trial of Vosaroxin and Cytarabine in Patients with First Relapsed or Refractory Acute Myeloid Leukemia
Sunesis Pharmaceuticals, Inc. announced results from the pivotal Phase III VALOR trial, a randomized, double-blind, placebo-controlled trial of vosaroxin and cytarabine in patients with first relapsed or refractory acute myeloid leukemia. [Sunesis Pharmaceuticals, Inc.] Press Release

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Postdoctoral Position – Molecular Properties of Leukemic Stem Cells (BC Cancer Agency)

Postdoctoral Position – Cell Signaling in Hematopoietic Stem Cells (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Position – Regenerative Effects of Some Mutations on Hematopoietic Stem Cells (Istanbul University Institute of Experimental Medicine)

Postdoctoral Fellow – Hematopoietic Stem Cells and Signaling Transduction (University of Pennsylvania)

Stem Cell Biology Program Director (Blood Research Institute of BloodCenter of Wisconsin)

Assistant or Associate Professor – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Research Associate – Cancer, Stem Cells, and Immunity Focusing on Membrane Proteins and Signaling Pathways (UT Southwestern Medical Center)

Postdoctoral Positions – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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