Hematopoiesis News Volume 5.25 | Jul 8 2014

Preclinical Evaluation of Echinomycin: Therapeutic Efficacy in Relapsed Acute Myeloid Leukemia without Adverse Effects on Host Hematopoietic Stem Cells
Investigators used a mouse model of relapsed acute myeloid leukemia (AML) to explore whether the HIF1α inhibitor Echinomycin can be used to treat relapsed AML without affecting host hematopoietic stem cells. [Blood] Abstract

Serpin Spi2A as a Novel Modulator of Hematopoietic Progenitor Cell Formation
Via loss-of-function studies, scientists define roles for an hematopoietin-regulated Serpina3g/Spi2A intracellular serpin during granulomyelocytic, B-cell and HSC formation. In granulomyelocytic progenitors, GMCSF strongly induced Serpina3g expression with Stat5-dependency. [Stem Cells] Abstract

Nitric Oxide-Induced Murine Hematopoietic Stem Cell Fate Involves Multiple Signaling Proteins, Gene Expression and Redox Modulation
The direct role of nitric oxide (NO^●), a reactive nitrogen species, in the modulation of hematopoiesis was investigated using two sources of NO^●, one produced by endothelial cells stimulated with carbachol in vitro and another using the NO^●-donor SNAP in vivo. [Stem Cells] Abstract

Potent Cooperation between the NUP98-NSD1 Fusion and FLT3-ITD Mutation in Acute Myeloid Leukemia Induction
The NUP98-NSD1 fusion, product of the t(5;11)(q35;p15.5) chromosomal translocation, is one of the most prevalent genetic alterations in cytogenetically normal pediatric acute myeloid leukemias and is associated with poor prognosis. Expression of NUP98-NSD1 provided mouse strain-dependent, aberrant self-renewal potential to bone marrow progenitor cells. [Haematologica] Full Article

Leucine-Rich Repeat-Containing G-Protein Coupled Receptor 5 Marks Short-Term Hematopoietic Stem and Progenitor Cells during Mouse Embryonic Development
The authors report the detection of Lgr5 expression in hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad-mesonephros and fetal liver. They also found that a portion of Lgr5⁺ cells expressed Runx-1 genes that are critical for the ontogeny of HSPCs. [J Biol Chem] Abstract | Full Article

Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells
Investigators identified the tumor suppressor GADD45G as an instructor of long-term repopulating hematopoietic stem cell differentiation under the control of differentiation-promoting cytokine receptor signaling. [Stem Cell Rep] Full Article | Graphical Abstract

CLINICAL RESEARCH

Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype
Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Researchers aimed to determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. [JAMA] Full Article | Press Release | Video

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial
High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in Phase I and small Phase II trials. Investigators compared efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. [JAMA]
Abstract | Press Release

Results from a Clofarabine-Busulfan Containing Reduced-Toxicity Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: The Phase II Prospective CLORIC Trial
Researchers prospectively evaluated the safety and efficacy of a clofarabine, intravenous busulfan and antithymocyte globulin-based reduced-toxicity conditioning regimen before allogeneic stem cell transplantation. [Haematologica] Abstract | Full Article

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

FDA Grants Spectrum Pharmaceuticals Accelerated Approval of Beleodaq™ (Belinostat) for Injection
Spectrum Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted Accelerated Approval of Beleodaq™ for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. [Spectrum Pharmaceuticals] Press Release

University of Pennsylvania’s Personalized Cellular Therapy for Leukemia Receives FDA’s Breakthrough Therapy Designation
A University of Pennsylvania-developed personalized immunotherapy has been awarded the U.S. Food and Drug Administration’s Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia. The investigational therapy, known as CTL019, is the first personalized cellular therapy for the treatment of cancer to receive this classification. [Penn Medicine] Press Release

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

NEW Biologist – Hypoxia Signaling in Myeloproliferative Neoplasms (University Hospital Aachen)

NEW Research Associate – Transcriptional/Epigenetic Changes and Their Roles in Normal and Malignant Hematopoietic Stem Cell Development (King’s College London)

NEW PhD Student – The Hematopoietic Niches in Bone (KU Leuven)

Scientific Manager – hES and iPS Cell Lines to Model Normal Hematopoiesis and Related Blood Diseases (St. Jude Children’s Research Hospital)

Postdoctoral Research Fellow – Cardiovascular Immunology / Hematology (Massachusetts General Hospital)

Research Associate – Hematopoietic and Leukemic Stem Cells (Shanghai Jiao-Tong University School of Medicine)

Clinical HSCT Faculty Position – Pediatric Hematology-Oncology (University of Wisconsin School of Medicine)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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