Hematopoiesis News 8.39 October 3, 2017 | |
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TOP STORYResearchers showed that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibited decreased competitiveness in vivo and were unable to rescue hematopoiesis in the setting of myelosuppression. [Cell Stem Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Cell-instructive hydrogel compartment arrays were used to analyze the response of human hematopoietic stem and progenitor cells to defined biomolecular and spatial cues. [Adv Mater] Abstract Investigators showed that adult HSCs are hypersensitive to low-dose irradiation. This hyper-radiosensitivity was dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promoted autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protected HSCs from the detrimental effects of ROS, but protection was transient, and increased ROS levels returned, promoting a long-term decrease in HSC self-renewal. [Cell Rep] Full Article | Graphical Abstract The authors describe a method to multiplex homologous recombination in human hematopoietic stem and progenitor cells and primary human T cells by combining rAAV6 donor delivery and the CRISPR/Cas9 system delivered as ribonucleoproteins. [eLife] Abstract | Full Article Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice Researchers found that mouse serum induces human red blood cell (hRBC) adherence to murine phagocytic cells, including professional phagocytic macrophages and neutrophils and non-professional phagocytic endothelial cells. Complement was found to be responsible for mouse-serum-induced hRBC adherence to murine phagocytic cells. [Stem Cell Reports] Full Article Grb2 Regulates the Proliferation of Hematopoietic Stem and Progenitors Cells The authors showed that growth factor receptor-bound protein 2 (Grb2) mRNAs are preferentially expressed in HSCs compared to progenitors and differentiated cells of the myeloid and erythroid lineages. Conditional deletion of Grb2 induced a rapid decline of erythroid and myeloid progenitors and a progressive decline of HSC numbers in steady state conditions. [Biochim Biophys Acta] Abstract Scientists tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity. Signaling through a control CR with a wild-type c-Mpl cytoplasmic tail sufficed to enhance HSC proliferation and colony formation in cooperation with stem cell factor. [Stem Cell Rev] Full Article CLINICAL RESEARCHAge of Red Cells for Transfusion and Outcomes in Critically Ill Adults In an international, multicenter, randomized, double-blind trial, the authors assigned critically ill adults to receive either the freshest available, compatible, allogeneic red cells or standard-issue, compatible, allogeneic red cells. The age of transfused red cells did not affect 90-day mortality among critically ill adults. [N Engl J Med] Full Article Of the patients who received hematologic stem cell transplantation, 30.8% responded to the treatment with a complete remission. The TLS–ERG transcript levels reflected MRD and might predict relapse and guide effective intervention. [Biol Blood Marrow Transplant] Abstract The authors explored mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. They evaluated levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous hematopoietic stem cell transplantation and examined their influence on hematological recovery. [Ann Hematol] Abstract | |
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REVIEWSIndications for and Adverse Effects of Red-Cell Transfusion Advances in clinical research have led to reduced use of blood products. Judicious use has reduced the incidence of lung injury and circulatory overload. Testing of blood products for infectious agents has reduced their transmission. [N Engl J Med] Abstract In addressing the current understanding of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA), the authors highlight the risk factors leading to endothelial damage and a pathophysiological cascade that ensues. They also compare the different definition criteria and biomarkers that can enable early intervention in TA-TMA patients. [Bone Marrow Transplant] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSSyros to Present Biomarker Data from Ongoing Phase II Clinical Trial of SY-1425 Syros Pharmaceuticals announced that the company will present biomarker data from its ongoing Phase II clinical trial of SY-1425, an oral first-in-class selective retinoic acid receptor alpha agonist, in genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome. [Press release from Syros Pharmaceuticals, Inc. discussing research to be presented at the European School of Haematology’s 4th International Conference on Acute Myeloid Leukemia ‘Molecular and Translational’: Advances in Biology and Treatment, Estoril] Press Release | |
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INDUSTRY NEWSThe University of Texas MD Anderson Cancer Center and Pfizer Inc. announced that they have entered into a clinical collaboration to study novel combinations of three Pfizer investigational immuno-oncology therapies and other Pfizer agents in the treatment of various solid tumors and hematologic malignancies. [The University of Texas MD Anderson Cancer Center] Press Release SELLAS Life Sciences Group, Ltd. announced entry into a Clinical Trial Collaboration and Supply Agreement for the conduct of a combination clinical trial targeting multiple cancer types with Merck & Co., Inc (MSD). SELLAS’ Wilms tumor-1-targeting peptide immunotherapeutic agent, galinpepimut-S, will be administered in combination with MSD’s anti-PD-1 therapy KEYTRUDA® in a Phase I/II trial enrolling patients in five cancer indications, including both hematologic malignancies and solid tumors. [SELLAS Life Sciences Group , Ltd.] Press Release UC Davis Receives $8 Million to Expand Access to Stem Cell Clinical Trials The California Institute for Regenerative Medicine awarded a nearly $8 million grant to University of California (UC), Davis, stem cell researchers to launch a special clinical trials program in Sacramento to accelerate the therapeutic development and delivery of stem cell therapies in human patients. [University of California, Davis] Press Release ASH Supports Promising Biomedical Research of Five Investigators through ASH Bridge Grant Program The American Society of Hematology (ASH) announced the names of five investigators whose research has been awarded $150,000 through the ASH Bridge Grant Program. Designed to sustain promising hematologic research proposals that score well but cannot be funded by the National Institutes of Health due to uncertain funding, these ASH Bridge Grants will ensure that potentially life-saving research continues at five institutions across the United States. [American Society of Hematology] Press Release Rigel Pharmaceuticals, Inc. announced that the company recently completed enrollment of Stage 1 of its Phase II, open-label, multi-center, two-stage study of its investigational drug fostamatinib for the treatment of patients with warm antibody AIHA. On a top-line, preliminary basis, the Phase II study has achieved the pre-specified primary efficacy endpoint for Stage 1. [Rigel Pharmaceuticals, Inc.] Press Release Sancilio Pharmaceuticals Company, Inc. announced the successful completion of a randomized, double blinded, placebo controlled clinical trial in pediatric sickle cell patients aged 5-17 years old. The clinical trial is a multi-center study designed to evaluate treatment effects and safety of Altemia™, a novel pharmaceutical preparation utilizing the company’s Advanced Lipid Technologies platform. [Sancilio Pharmaceuticals Company, Inc.] Press Release Celyad Reports a First Complete Response in a Relapsed Refractory AML Patient in the THINK Trial Celyad announced early clinical results of the first dose-level in the hematological arm of its THINK trial (THerapeutic Immunotherapy with CAR-T NKG2D). [Celyad] Press Release Sangamo Therapeutics, Inc. and Bioverativ Inc. announced that the FDA has accepted the Investigational New Drug (IND) application for ST-400, a gene-edited cell therapy candidate for people with transfusion-dependent beta-thalassemia. [Sangamo Therapeutics, Inc.] Press Release Aravive Receives Innovator of the Year Award from YTEXAS Aravive Biologics, Inc. has been honored as the 2017 “Innovator of the Year” by YTEXAS, which hosted its 4th Annual YTEXAS RēLO AWARDS. [Aravive Biologics, Inc.] Press Release | |
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POLICY NEWSAfter Upheaval, Russian Academy of Sciences Gets New Leader After months of uncertainty, the Russian Academy of Sciences finally has a new leader. Russian President Vladimir Putin approved physicist Alexander Sergeyev as the academy’s president for the next five years. Sergeyev has vowed to secure more money for Russian science and create a fund, through a new tax on fossil fuel company profits, for upgrading the country’s antiquated research infrastructure. [ScienceInsider] Editorial Researchers Caught in Growing Rift over Catalan Independence Scientists in Catalonia are feeling the ripples of a severe crisis as the region’s bid for independence from Spain comes to a head. [ScienceInsider] Editorial French Government Proposes Big Science-Spending Boost French research funding is set for a heartening increase in the country’s first budget under President Emmanuel Macron, if draft 2018 plans are voted into law. [Nature News] Editorial
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EVENTSNEW 7th in Leukemia Research (NDLR) Meeting Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Hematopoietic Stem Cells (Memorial Sloan Kettering Cancer Center) NEW Staff Scientist – Translational Hematology (University of Copenhagen) Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University) Scientist – Hematopoietic Precursors and Immune Cells (Università di Genova) Postdoctoral Opportunities – Biology of Colorectal Cancer (Albert Einstein College of Medicine) Postdoctoral Fellow – Cancer Biology (UCSF Benioff Children’s Hospital) Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine) Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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