Hematopoiesis News Volume 3.42 | Oct 23 2012

LABORATORY RESEARCH

The Requirement for Cyclin D Function in Tumor Maintenance
To test the efficacy of targeting D-cyclins in cancer treatment, researchers engineered mouse strains that allowed acute and global ablation of individual D-cyclins in a living animal. Ablation of cyclin D3 in mice bearing Notch1-driven T cell acute lymphoblastic leukemias triggered tumor cell apoptosis. [Cell Canc Cell]
Abstract | Press Release

Vascular Niche E-Selectin Regulates Hematopoietic Stem Cell Dormancy, Self Renewal and Chemoresistance
Scientists report a new role for the adhesion molecule E-selectin expressed exclusively by bone marrow endothelial cells in the vascular hematopoietic stem cells (HSC) niche. HSC quiescence was enhanced and self-renewal potential was increased in E-selectin knockout mice or after administration of an E-selectin antagonist, demonstrating that E-selectin promotes HSC proliferation and is a crucial component of the vascular niche. [Nat Med] Abstract | Press Release

CaMKII γ, a Critical Regulator of Chronic Myeloid Leukemia Stem/Progenitor Cells, Is a Target of the Natural Product Berbamine
Scientists described the unknown activity of the natural product berbamine that efficiently eradicates leukemia stem cells and T315I mutant Bcr-Abl clones. They identified CaMKII γ as a specific and critical target of berbamine for its anti-leukemia activity. [Blood] Abstract

In Situ Production of Innate Immune Cells in Murine White Adipose Tissue
Scientists prospectively isolated a peculiar hematopoietic stem/progenitor cell population from murine white adipose tissue. The cells are phenotypically similar to bone marrow-hematopoietic stem cells, and are able to differentiate into both myeloid and lymphoid lineages in vitro. [Blood] Abstract

TNF-α Has Tropic Rather Than Apoptotic Activity in Human Hematopoietic Progenitors: Involvement of TNF Receptor-1 and Caspase-8
Investigators assessed the influences of TNF-α and its two cognate receptors on the function of fresh umbilical cord blood and cryopreserved mobilized peripheral blood. CD34⁺ progenitors from both sources are less susceptible to spontaneous apoptosis than lineage-committed cells, and are not induced into apoptosis by TNF-α. [Stem Cells] Abstract

Comparison of Hematopoietic Stem Cells Derived from Fresh and Cryopreserved Whole Cord Blood in the Generation of Humanized Mice
Scientists compared the efficiency of CD34⁺ stem cells isolated from cryopreserved cord blood from a blood bank and fresh cord blood in generating highly engrafted humanized mice in NOD-SCID IL2Rγ^null rodents. [PLoS One] Full Article

Systemic Delivery of Triplex-Forming PNA and Donor DNA by Nanoparticles Mediates Site-Specific Genome Editing of Human Hematopoietic Cells In Vivo
Investigators demonstrated site-specific gene editing of human cells in vivo in hematopoietic stem cell-engrafted NOD.Cg-Prkdc^scidIL2rγ^tm1Wjl mice, using biodegradable nanoparticles loaded with triplex-forming peptide nucleic acids (PNAs) and single-stranded donor DNA molecules. [Gene Ther] Abstract

An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response
Researchers report an in vivo gain-of-function screen and the identification of microRNA-150 (miR-150) as an inhibitor of hematopoietic recovery upon 5-fluorouracil-induced injury. [Cell Reports]
Full Article | Press Release | Graphical Abstract

CLINICAL RESEARCH

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors
Researchers conducted a phase III, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare two-year survival probabilities with the use of an intention-to-treat analysis. [N Engl J Med] Abstract | Press Release

Fludarabine, Cytarabine, and Attenuated-Dose Idarubicin Combination Therapy for Elderly Acute Myeloid Leukemia Patients
Researchers performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin regimen in elderly acute myeloid leukemia patients. [Am J Hematol] Abstract

B-Lineage Transcription Factors and Cooperating Gene Lesions Required for Leukemia Development
The authors provide a detailed overview of the genetic pathways that interact with these B-lineage specification factors, and describe how mutations affecting these master regulators together with cooperating lesions drive leukemia development. [Leukemia] Abstract

The Biochemistry of Hematopoietic Stem Cell Development
The authors focus on the biochemistry behind the generation of potent long-lived self-renewing stem cells of the blood system. Both the intrinsic and extrinsic regulators that affect the generation, maintenance and expansion of hematopoietic stem cells in the embryo are discussed. [Biochim Biophys Acta] Abstract

Lymphoma Specialized Programs of Research Excellence Grant Renewed through Baylor College of Medicine, The Methodist Hospital, Texas Children’s Hospital Center for Cell and Gene Therapy
The Center for Cell and Gene Therapy at Baylor College of Medicine, The Methodist Hospital and Texas Children’s Hospital has received an $11.5 million, five-year grant from the National Cancer Institute to continue advancing translational lymphoma research by developing and testing new forms of T-cell immunotherapies to fight the disease. [Baylor College of Medicine] Press Release

Association Establishes the AABB Center for Cellular Therapies
AABB (formerly the American Association of Blood Banks) has established the AABB Center for Cellular Therapies, a functional unit within AABB that will focus on activities designed to foster patient safety and responsible innovation in the cellular therapy and regenerative medicine field. [AABB] Press Release

The C4C Consortium Announces the Implementation of France’s First Ever Facility for the Industrialization of Cell Therapeutics and Presents the Five Drugs under Development for Use in Personalized Medicine
The C4C consortium today announced the implementation of France’s first ever dedicated technical facility for the manufacture of cell therapy products. The C4C project brings together two biotech companies and seven public-sector organizations and university medical centers. [Business Wire] Press Release

Actinium Pharmaceuticals Announces Johns Hopkins University School of Medicine Joins Multicenter Phase I/II Actimab-A Trial
Actinium Pharmaceuticals, Inc. announced that Johns Hopkins University School of Medicine in Baltimore, MD has joined the company’s ongoing phase I/II trial in newly diagnosed elderly patients with acute myeloid leukemia.  [Actinium Pharmaceuticals, Inc.] Press Release

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Postdoctoral Position – Impact of Inflammation on Hematopoiesis and Cancer (University of Murcia)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

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