Hematopoiesis News Volume 4.27 | Jul 16 2013

Myeloproliferative Neoplasia Remodels the Endosteal Bone Marrow Niche into a Self-Reinforcing Leukemic Niche
Scientists showed that myeloproliferative neoplasia progressively remodels the endosteal bone marrow (BM) niche into a self-reinforcing leukemic niche that impairs normal hematopoiesis, favors leukemic stem cell function, and contributes to BM fibrosis. [Cell Stem Cell] Abstract | Graphical Abstract

EVI1 Oncoprotein Interacts with a Large and Complex Network of Proteins and Integrates Signals through Protein Phosphorylation
Ecotropic viral integration site-1 (EVI1) is an oncogenic zinc finger transcription factor whose expression is frequently up-regulated in myeloid leukemia and epithelial cancers. To better understand the mechanisms underlying EVI1-associated disease, researchers sought to define the EVI1 interactome in cancer cells. [Proc Natl Acad Sci USA] Abstract

Clonal Precursor of Bone, Cartilage, and Hematopoietic Niche Stromal Cells
Researchers described a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bone marrow tissue of fetal, neonatal, and adult mice. Within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including hematopoietic stem cell supportive 6C3(+) niche cells. [Proc Natl Acad Sci USA] Abstract

Epigenetic Silencing of Bim Transcription by Spi-1/PU.1 Promotes Apoptosis Resistance in Leukemia
Investigators showed that Spi-1 inhibits mitochondrial apoptosis in vitro and in vivo through the transcriptional repression of Bim, a proapoptotic factor. BIM interacts with MCL-1 that behaves as a major player in the survival of the preleukemic cells. [Cell Death Differ] Abstract

Acat1 Gene Ablation in Mice Increases Hematopoietic Progenitor Cell Proliferation in Bone Marrow and Causes Leukocytosis
Researchers investigated the role of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) in hematopoiesis. They tested the hypothesis that global Acat1^-/- may affect hematopoiesis, rather than affecting macrophage function only, and showed that Acat1^-/- mice contain significantly higher numbers of myeloid cells and other cells than wild-type mice. [Arterioscler Thromb Vasc Biol] Abstract

Transgenic Expression of BRCA1 Disturbs Hematopoietic Stem and Progenitor Cells Quiescence and Function
Scientists generated BRCA1 transgenic mice to investigate the effects of BRCA1 on the mechanisms of quiescence and differentiation in hematopoietic stem cells. [Exp Cell Res] Abstract

Blood Cell-Derived Induced Pluripotent Stem Cells Free of Reprogramming Factors Generated by Sendai Viral Vectors
Using nonintegrating cytoplasmic Sendai viral vectors, researchers generated induced pluripotent stem cells (iPSCs) efficiently from adult mobilized CD34⁺ and peripheral blood mononuclear cells. Using the spin embryoid body method, they showed that these blood cell-derived iPSCs could efficiently be differentiated into hematopoietic stem and progenitor cells without the need of coculture with either mouse or human stromal cells. [Stem Cells Transl Med] Abstract | Press Release

CLINICAL RESEARCH

Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy
The authors used a lentiviral vector to transfer a functional arylsulfatase A (ARSA) gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile metachromatic leukodystrophy. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. [Science]
Abstract | Press Release

Hematopoietic Progenitor Cell Collection after Autologous Transplant for Multiple Myeloma: Low Platelet Count Predicts for Poor Collection and Sole Use of Resulting Graft Enhances Risk of Myelodysplasia
Collection of hematopoietic progenitor cells after previous autologous hematopoietic progenitor cell transplant was studied in 221 patients with multiple myeloma. [Leukemia] Abstract

Impact of Donor Source on Hematopoietic Cell Transplantation Outcomes for Patients with Myelodysplastic Syndromes (MDS)
Allogeneic hematopoietic cell transplantation (HCT) from human leukocyte antigen matched related donor and matched unrelated donors produces similar survival for patients with acute myelogenous leukemia. Whether these results can be extended to patients with MDS is unknown. Therefore, a disease-specific analysis of post-HCT outcomes for MDS was performed. [Blood] Abstract

Biomechanical Force in Blood Development: Extrinsic Physical Cues Drive Pro-Hematopoietic Signaling
The authors present an overview of the sensors and intracellular signaling pathways activated by mechanical cues and highlight the role of mechanotransductive pathways in hematopoiesis. [Differentiation] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoietic research field.

New Drug Application Submitted to U.S. FDA for Ibrutinib in the Treatment of Two B-Cell Malignancies
Janssen Research & Development, LLC announced the submission of a New Drug Application for ibrutinib to the U.S. Food and Drug Administration (FDA) for its use in the treatment of previously treated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, and for its use in the treatment of previously treated patients with mantle cell lymphoma. [Johnson & Johnson Services, Inc.] Press Release

Calimmune Initiates HIV Stem Cell Study at Two California Research Sites
Calimmune announced that the first patient has begun treatment in a Phase I/II clinical trial designed to determine whether a pioneering genetic medicine approach can help to protect individuals infected with HIV from the effects of the virus. The study, “Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection,” utilizes a gene medicine called Cal-1, developed in the lab of Nobel Laureate Dr. David Baltimore and by Calimmune. In the study, 12 HIV-positive participants will be infused with their own T cells and stem cells (hematopoietic stem cells), which have been modified to block the HIV receptor CCR5, and to prevent HIV fusion. [Calimmune] Press Release

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

Postdoctoral Fellow – Cancer Stem Cell Biology (McGill University)

Postdoctoral Position – Hematopoietic Differentiation of Pluripotent Stem Cells (Center for Physiology and Pathophysiology, University of Cologne)

Research Associate (Assistant Professor) – Pediatric Hematology/Oncology (The University of Chicago)

Postdoctoral Research Fellow – Hematology/Pharmacology (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Positions – Stem Cell Biology and Epigenetics (University of Wisconsin-Madison)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

PhD Student Position – Hematopoietic Stem Cells (Katholieke Universiteit Leuven)

Postdoctoral Fellow – Radiobiology and Hematopoietic Stem Cell Biology (Indiana University School of Medicine)

Postdoctoral Researcher – Hematopoietic Stem Cells (Albert Einstein College of Medicine)

Studentship – Novel Mechanisms in Blood Cancers Drug-Resistance (University of East Anglia)

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