Hematopoiesis News Volume 3.28 | Jul 17 2012

LABORATORY RESEARCH

The Blk Pathway Functions as a Tumor Suppressor in Chronic Myeloid Leukemia Stem Cells
Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for cancer stem cells, researchers showed that BCR-ABL downregulates the B-lymphoid kinase (Blk) gene through c-Myc in leukemic stem cells (LSCs) in CML mice and that Blk functions as a tumor suppressor in LSCs but does not affect normal hematopoietic stem cells or hematopoiesis. [Nat Genet] Abstract

Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53
The results identify selective inhibition of ribosomal RNA gene transcription as a therapeutic strategy for the cancer specific activation of p53 and treatment of hematologic malignancies. [Cancer Cell] Abstract | Press Release

Targeting CDK1 Promotes FLT3-Activated Acute Myeloid Leukemia Differentiation through C/EBPα
Scientists found that inhibition of cyclin-dependent kinase 1 (CDK1) activity relieves the differentiation block in cell lines with mutated fms-like tyrosine kinase 3 (FLT3) as well as in primary patient-derived peripheral blood samples. [J Clin Invest] Full Article

FGF Signaling Facilitates Post-Injury Recovery of Mouse Hematopoietic System
Researchers examined fibroblast growth factor (FGF) receptor 1 expression and investigated its in vivo function in hematopoietic stem and progenitor cells. [Blood] Abstract

Ex Vivo Expansion of Normal and Chronic Myeloid Leukemic Stem Cells without Functional Alteration Using a NUP98HOXA10homeodomain Fusion Gene
Researchers compared the number of long-term culture-initiating cells present in cultures of lenti-NUP98HOXA10homeodomain versus control virus-transduced CD34⁺ cells originally isolated from human cord blood and chronic phase chronic myeloid leukemia patients. [Leukemia] Abstract

Mcl-1 and Bcl-xL Regulate Bak/Bax-Dependent Apoptosis of the Megakaryocytic Lineage at Multistages
Anti-apoptotic Bcl-2 family proteins are involved in the survival of various hematopoietic lineages and are often dysregulated in hematopoietic malignancies. Here, researchers describe the crucial anti-apoptotic role of Mcl-1 and Bcl-xL in the megakaryocytic lineage at multistages. [Cell Death Differ] Abstract

Cord Blood-Hematopoietic Stem Cell Expansion in Three-Dimensional Fibrin Scaffolds with Stromal Support
Four different three-dimensional biomaterial scaffolds were tested for freshly isolated cord blood-CD34⁺ cell expansion in presence of efficient exogenous cytokine supplementation and umbilical cord-mesenchymal stem cells. [Biomaterials] Abstract

Dynamics of Human Prothymocytes and Xenogeneic Thymopoiesis in Hematopoietic Stem Cell-Engrafted Nonobese Diabetic-SCID/IL-2rγ^null Mice
To model the developmental pattern of human prothymocytes and thymopoiesis, researchers used NOD-scid/γc^-/- mice grafted with human umbilical cord blood CD34⁺ hematopoietic progenitor cells. [J Immunol] Abstract

Suppression of Homeobox Transcription Factor VentX Promotes Expansion of Human Multipotent Hematopoietic Stem/Progenitor Cells
Researchers report that VentX expression is up-regulated during ontogenesis of human hematopoietic cells. They showed that VentX regulates critical cell cycle regulators and Wnt downstream genes previously implicated in human multipotent hematopoietic stem progenitor cell proliferation and expansion. [J Biol Chem] Abstract | Full Article

PDCD2 Controls Hematopoietic Stem Cell Differentiation during Development
Scientists suggest that programmed cell death 2 (Pdcd2) plays a critical role in regulating the transcriptional hierarchy controlling hematopoietic lineage determination, and that the effects of pdcd2 in regulating mitotic cell death may contribute to its role(s) in directing hematopoietic differentiation during development. [Stem Cells Dev] Abstract

CLINICAL RESEARCH

Blockade of Lymphocyte Chemotaxis in Visceral Graft-versus-Host Disease
Investigators enrolled 38 high-risk patients in a single-group phase I and II study of reduced-intensity allogeneic hematopoietic stem-cell transplantation that combined maraviroc with standard graft-versus-host disease prophylaxis. [N Engl J Med] Abstract

MK-0457, an Aurora Kinase and BCR-ABL Inhibitor, Is Active in Patients with BCR-ABL T315I Leukemia
MK-0457 was studied in a Phase I/II study on 77 patients with refractory hematologic malignancies. [Leukemia] Abstract

NOXXON Initiates Phase IIa of Anti-CXCL12/SDF-1 Spiegelmer^® NOX-A12 for Treatment of Chronic Lymphocytic Leukemia
NOXXON Pharma announced the treatment of the first cohort of three chronic lymphocytic leukemia patients in a Phase IIa clinical trial of its NOX-A12 anti-CXCL12/SDF-1 (CXC Chemokine Ligand 12/Stromal Cell-Derived Factor-1) Spiegelmer^®. [NOXXON Pharma AG] Press Release

Actinium Pharmaceuticals, Inc. Licenses Monoclonal Antibody from Fred Hutchinson Cancer Research Center
Actinium Pharmaceuticals, Inc. and Fred Hutchinson Cancer Research Center announced that they have signed an exclusive worldwide license agreement for BC8, an investigational monoclonal antibody developed to target and eradicate cancerous and other white blood cells in preparation for a hematopoietic stem cell transplantation. [Actinium Pharmaceuticals, Inc.] Press Release

Alex’s Lemonade Stand Grants Support BCM Childhood Cancer Researchers
Three Baylor College of Medicine (BCM) researchers received support totaling $500,000 from the nonprofit organization Alex’s Lemonade Stand Foundation for their work to find more effective treatments for childhood cancer. The grant funding to Goodell will support her research on the role the gene LYL1 plays in T-Cell ALL, one of the most frequent types of childhood leukemia. [Baylor College of Medicine]
Press Release

Noted Leukemia Clinician, Researcher Named UI Cancer Center Director
Dr. Howard Ozer has been named director of the University of Illinois (UI) Cancer Center. Ozer is internationally known for research in the development of hematopoietic growth factors and cytokines and for clinical trials in leukemia and lymphoma. [University of Illinois] Press Release

Biomedical Engineering Degree First in Western Canada
The University of Victoria is launching a new undergraduate biomedical engineering degree, the first of its kind west of Ontario. [University of Victoria] 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)

NEW University of Oxford: Stem Cells – A Pathway Through the Maze
December 5-7, 2012
Oxford, United Kingdom

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Postdoctoral Position – Anti-HIV Hematopoietic Stem Cell Gene Therapy (University of California, Los Angeles)

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Postdoctoral Positions – Stem Cells and Immunology (University of Connecticut)

Postdoctoral Position – Stem Cells (Children’s Hospital of Chicago Research Center)

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