Hematopoiesis News Volume 4.11 | Mar 26 2013

LABORATORY RESEARCH

Characterization of Transcriptional Networks in Blood Stem and Progenitor Cells Using High-Throughput Single-Cell Gene Expression Analysis
Researchers determined the expression of a network of 18 key hematopoietic transcription factors in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. They demonstrated that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through comprehensive bioinformatic analysis revealed positively and negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, Gfi1 and Gfi1b. [Nat Cell Biol] Abstract

Endothelio-Mesenchymal Interaction Controls runx1 Expression and Modulates the notch Pathway to Initiate Aortic Hematopoiesis
Hematopoietic stem cells (HSCs) are produced by a small cohort of hemogenic endothelial cells (ECs) during development through the formation of intra-aortic hematopoietic cell (HC) clusters. The Runx1 transcription factor plays a key role in the EC-to-HC and -HSC transition. Investigators showed that Runx1 expression in hemogenic ECs and the subsequent initiation of HC formation are tightly controlled by the subaortic mesenchyme, although the mesenchyme is not a source of HCs. [Dev Cell] Abstract

Reducing TMPRSS6 Ameliorates Hemochromatosis and β-Thalassemia in Mice
Researchers identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. [J Clin Invest] Full Article | Press Release

An Epigenetic Component of Hematopoietic Stem Cell Aging Amenable to Reprogramming into a Young State
The authors applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, they functionally characterized iPS-derived hematopoietic stem cells (HSCs) in primary chimeras and following the transplantation of ‘re-differentiated’ HSCs into new hosts; the gold standard to assess HSC function. [Blood] Abstract | Press Release

Improved Ex Vivo Expansion of Adult Hematopoietic Stem Cells by Overcoming CUL4-Mediated Degradation of HOXB4
Direct transduction of the homeobox protein HOXB4 promotes the proliferation of hematopoietic stem cells (HSCs) without induction of leukemogenesis, but requires frequent administration to overcome its short protein half-life (~1 hour). Researchers demonstrated that HOXB4 protein levels are post-translationally regulated by the CUL4 ubiquitin ligase, and define the degradation signal sequence of HOXB4 required for CUL4-mediated destruction. [Blood] Abstract | Press Release

Targeting Chronic Lymphocytic Leukemia Cells with a Humanized Monoclonal Antibody Specific for CD44
The authors found that a humanized mAb specific for CD44 (RG7356) was directly cytotoxic for leukemia B cells, but had little effect on normal B cells. Moreover, RG7356 could induce chronic lymphocytic leukemia cells that expressed the zeta-associated protein of 70 kDa to undergo caspase-dependent apoptosis, independent of complement or cytotoxic effector cells. [Proc Natl Acad Sci USA] Abstract | Press Release

Preferential Eradication of Acute Myelogenous Leukemia Stem Cells by Fenretinide
Based on in vitro and in vivo evidence, researchers report that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating leukemia stem cells but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. [Proc Natl Acad Sci USA] Abstract

MyD88 Signaling in CD4 T Cells Promotes IFN-γ Production and Hematopoietic Progenitor Cell Expansion in Response to Intracellular Bacterial Infection
Scientists investigated the signals that activate hematopoietic stem and progenitor cells (HSPCs) during ehrlichiosis, a disease characterized by profound hematopoietic dysfunction in both humans and mice. In a mouse model of ehrlichiosis, they observed that infection-induced proliferation of bone marrow HSPCs was dependent on IFN-γ signaling and was partially dependent on MyD88. [J Immunol] Abstract

CLINICAL RESEARCH

Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia
Two children with relapsed and refractory pre-B-cell acute lymphoblastic leukemia received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10⁶ to 1.2×10⁷ CTL019 cells per kilogram of body weight. [N Engl J Med]
Abstract | Press Release

Long-Term Survival after Allogeneic Hematopoietic Cell Transplantation for AML in Remission: Single-Centre Results after TBI-Based Myeloablative and Non-Myeloablative Conditioning
Investigators report the results of non-myeloablative and myeloablative conditioning for hematopoietic cell transplantation in 207 consecutive AML patients at a single institution. [Bone Marrow Transplant] Abstract

With Philanthropy, Research Team Targets a Biological Drug for Treating Leukemia
Innovative research, led in tandem by Masonic Cancer Center members Michael Verneris, M.D. and Daniel Vallera, Ph.D., focuses on a bioengineered molecule that has the ability to hitch two of the body’s cells together: one, the cancer cell, and the other, a natural killer cell. [University of Minnesota] Press Release

ARIAD Announces That Iclusig™ (Ponatinib) Receives Positive CHMP Opinion for Approval in the European Union
ARIAD Pharmaceuticals, Inc. announced that the Committee for Human Medicinal Products (CHMP) of the European Medicines Agency has adopted a positive opinion on the marketing authorization application for Iclusig™ for two indications. [ARIAD Pharmaceuticals, Inc.] Press Release

Gentium Receives Negative Opinion from the CHMP on Defibrotide for the Treatment and Prevention of VOD
Gentium S.p.A. announced that it has been informed by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) that it has adopted a negative opinion, recommending the refusal of the marketing authorization for Defibrotide to treat and prevent hepatic venoocclusive disease (VOD) in adults and children undergoing hematopoietic stem cell transplantation therapy. [Gentium S.p.A.]
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 Clinical Trials: Moving Stem Cell Based Therapies to the Clinic
April 15, 10:00AM (PT in US)
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NEW The 2013 Stem Cell Event Trilogy
June 4-6, 2013
London, United Kingdom

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

Postdoctoral Position – Stem Cell Research (University of Washington)

Postdoctoral Position – Hematopoietic Stem Cells and Stem Cell Aging (Cincinnati Children’s Hospital Research Foundation)

Lecturer or Reader – Associate Professor (University of Reading)

Research Assistant – Stem Cell & Leukemia Epigenetics (King’s College London)

Postdoctoral Position – Bioinformatics and Stem Cell Biology (University of Texas at Houston)

Postdoctoral Position – Stem Cells and Cancer (Tsinghua University)

Cord Blood Laboratory Manager (Puget Sound Blood Center)

Stem Cell Program Director (Cancer Treatment Centers of America)

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