Volume 4.02 | Jan 22

Hematopoiesis News 4.02 January 22, 2013
Hematopoiesis News

     In this issue: Publications | ReviewsIndustry News | Policy News | Events | Jobs
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TOP STORY
A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition
To elucidate splice-isoform regulators of human blast crisis (BC) leukemia stem cells (LSC) maintenance, scientists performed whole-transcriptome RNA sequencing, splice-isoform-specific quantitative RT-PCR, nanoproteomics, stromal coculture, and BC LSC xenotransplantation analyses. [Cell Stem Cell]
Abstract | Graphical Abstract | Press Release

New StemSpan(TM) SFEM II - for optimal CD34+ cell expansion of bone marrow and cord blood cells
PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo
Investigators described a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia. The expression of protein kinase C-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. [Cancer Cell] Full Article

The Rac GTPase Effector p21 Activated Kinase Is Essential for Hematopoietic Stem/Progenitor Cell Migration and Engraftment
Using conditional knock-out mice, researchers demonstrated that among group A p21 activated kinases (PAKs), Pak2-/- hematopoietic stem and progenitor cell (HSPC) show reduced homing to the bone marrow and altered cell shape similar to Pak Inhibitory Domain-LinSca1+c-kit+ cells in vitro and are completely defective in HSPC engraftment. [Blood] Abstract

Glypican-3 Mediated Inhibition of CD26 by TFPI: A Novel Mechanism in Hematopoietic Stem Cell Homing and Maintenance
CD26 is a widely expressed membrane-bound ectopeptidase that cleaves CXCL12 thereby depleting its chemokine activity. The authors identified tissue factor pathway inhibitor (TFPI) as a biological inhibitor of CD26 in murine and human hematopoietic stem/progenitor cells. [Blood] Abstract

Inhibition of Intracellular Dipeptidyl Peptidases 8 and 9 Enhances Parthenolide’s Anti-Leukemic Activity
Parthenolide is selectively toxic to leukemia cells; however, it also activates cell protective responses which may limit its clinical application. Therefore, scientists sought to identify agents that synergistically enhance parthenolide’s cytotoxicity. [Leukemia] Abstract

Tenovin-D3, a Novel Small-Molecule Inhibitor of Sirtuin SirT2, Increases p21 (CDKN1A) Expression in a p53-Independent Manner
Recent studies demonstrated that tenovin-6, a small molecule inhibitor of sirtuins SirT1 and SirT2, reduces tumor growth in vivo and eliminates leukemic stem cells in a murine model for chronic myelogenous leukemia. Here, researchers described a tenovin analog, tenovin-D3, that preferentially inhibits sirtuin SirT2 and induces predicted phenotypes for SirT2 inhibition. [Mol Cancer Ther] Abstract

Hoxa9 Transduction Induces Hematopoietic Stem and Progenitor Cell Activity through Direct Down-Regulation of Geminin Protein
Researchers found that retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. [PLoS One] Full Article

Combination of Guanine Arabinoside and Bcl-2 Inhibitor YC137 Overcomes the Cytarabine Resistance in HL-60 Leukemia Cell Line
Investigators established a new cytarabine (ara-C)-resistant acute myeloid leukemia cell line (HL-60/ara-C60) with dual resistance characteristics of the anti-antimetabolic character of decreased ara-C triphosphate production and an increase in the antiapoptotic factors Bcl-2 and Bcl-XL. [Cancer Sci] Abstract

CLINICAL RESEARCH

Impact of Malignant Stem Cell Burden on Therapy Outcome in Newly Diagnosed Chronic Myeloid Leukemia Patients
Researchers prospectively analyzed the proportion of Philadelphia chromosome positive leukemic stem and progenitor cells from 46 newly diagnosed chronic myeloid leukemia patients both at the diagnosis and during imatinib or dasatinib therapy. [Leukemia] Abstract

A Phase Ib GOELAMS Study of the mTOR Inhibitor RAD001 in Association with Chemotherapy for AML Patients in First Relapse
The authors conducted a Phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse. [Leukemia] Abstract

Complimentary Wallchart: Human Hematopoietic Progenitors. Request Your Copy Today.

REVIEWS
Has Umbilical Cord Blood Transplantation for AML Become Mainstream?
The authors discuss outcomes after umbilical cord blood transplantation for patients with acute myeloid leukemia (AML) and compare these outcomes to results after transplantation of other allogeneic graft sources. [Curr Opin Hematol] Abstract
INDUSTRY NEWS

University of Pennsylvania Joins Actinium Pharmaceuticals’ Multicenter Actimab-A Trial
Actinium Pharmaceuticals, Inc. (API) announced that the University of Pennsylvania Health System has joined the Company’s ongoing Phase I/II trial in newly diagnosed elderly patients with acute myeloid leukemia (AML). The trial is designed to establish the safety and efficacy of API’s drug Actimab-A in AML patients over the age of 60. [Actinium Pharmaceuticals, Inc.] Press Release

Northwestern Medicine Plans $1 Billion Research Investment
Leaders of Northwestern Medicine, comprising Northwestern University Feinberg School of Medicine, Northwestern Medical Faculty Foundation and Northwestern Memorial HealthCare, announced they have made a transformational commitment of more than $1 billion toward creating a leading medical research enterprise on Northwestern’s campus in Chicago’s Streeterville neighborhood. [Northwestern University] Press Release

POLICY NEWS

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)

EVENTS

NEW Keystone Symposia on Molecular and Cellular Biology: Molecular Clockworks and the Regulation of Cardio-Metabolic Function
April 3-7, 2013
Snowbird, United States

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

JOB OPPORTUNITIES

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Postdoctoral Fellow – Hematopoietic Stem Cells and Cancer (Tsinghua University)

Postdoctoral Fellow – Donor/Recipient Matching for Hematopoietic Stem Cell Transplantation (Cleveland Clinic Transplant Center)

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

Principal Investigator – Hematology / Oncology (Celgene Corporation)

Postdoctoral Position – Cell Metabolism and Programmed Cell Death in Leukemia and Solid Tumor Environments (University of Cincinnati)

Associate Research Scientist – Cancer Biology of Myelodysplastic Syndromes (Columbia University Medical Center)

PhD Studentship – Functional Genomic Analysis on Hematopoietic Stem Cells (Fritz Lipmann Institute)

PhD Studentship – Initiation and Progression of a Pre-Leukemic Mouse Model of AML (University of Ulm)


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