Hematopoiesis News 8.32 August 15, 2017 | |
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TOP STORYInvestigators analyzed deep-coverage, targeted, next-generation sequencing data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of clonal hematopoiesis (CH) in patients with non-hematologic malignancies. They identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations. [Cell Stem Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The Non-Coding RNA Landscape of Human Hematopoiesis and Leukemia Scientists present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, they identified unique fingerprint non-coding RNAs—such as LINC00173 in granulocytes—and assigned these to critical regulatory circuits involved in blood homeostasis. [Nat Commun] Full Article Using single-cell multigene expression analysis and time-lapse microscopy, researchers defined gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors, and analyzed systematically single HSC fate choices in culture. Their analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell–cell interaction signals in the niche. [Nat Commun] Full Article Scientists defined the role of the miR–146a–Traf6 signaling axis in the regulation of immune homeostasis using a genetic epistasis analysis in miR-146a−/− mice. They uncovered a separation of functions at the level of miR-146a targets. [Proc Natl Acad Sci USA] Abstract Researchers characterized zebrafish caudal hematopoietic tissue (CHT) and identified an important cellular and molecular mechanism of hematopoietic stem and progenitor cell (HSPC) expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells, and their migration and expansion display caudal vein-specific orientation in the CHT. [Dev Cell] Abstract | Graphical Abstract To better understand the gene networks that control this process, scientists investigated the role of the transcription factor HEB (TCF12) by disrupting the TCF12 gene locus in human embryonic stem cells (hESCs) and inducing them to differentiate toward hematopoietic outcomes. HEB-deficient hESCs retained key features of pluripotency, including expression of SOX2 and SSEA-4 and teratoma formation, while NANOG expression was reduced. [Stem Cell Reports] Full Article | Graphical Abstract Infection-Adapted Emergency Hematopoiesis Promotes Visceral Leishmaniasis The authors examined the bone marrow outcome of chronic visceral leishmaniasis and showed that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Their results suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. [PLoS Pathog] Full Article Scientists explored whether innovative combinations of small molecules can sufficiently, after short culture, expand adult HSCs while retaining their functionality in vivo. They found that five-day cultured cells in the presence of the small molecule combinations tested, achieved higher engraftment levels in NSG mice than both their uncultured and their cytokine only-cultured counterparts. [Stem Cells Transl Med] Full Article Tough Decoy Targeting of Predominant let–7 miRNA Species in Adult Human Hematopoietic Cells The authors hypothesized that focused targeting of individual let–7 miRNA family members would exhibit regulatory effect on hemoglobin expression in human adult erythroblasts. To study the effects of let–7 miRNAs upon globin expression, a lentiviral construct that incorporated the tough decoy design to target let–7a or let–7b was compared with empty vector controls. [J Transl Med] Full Article CLINICAL RESEARCHInvestigators examined immune cell subset counts and immunoglobulins in 81 severe aplastic anemia patients from day 30 to day 365 after haploidentical stem cell transplantation. Simultaneously, they determined which factors influence immune recovery and analyzed the effects of immune cell subsets on transplant outcomes. [Bone Marrow Transplant] Abstract Using the Transplant Registry Unified Management Program, researchers identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. [Bone Marrow Transplant] Abstract | |
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REVIEWSHSC Niche Biology and HSC Expansion Ex Vivo Scientists discuss current knowledge of niche biology, the intrinsic regulators of HSC self-renewal in vivo, and introduce novel niche-informed strategies of HSC expansion ex vivo. [Trends Mol Med] Abstract The authors discuss the changing landscape of genome editing in HSCs from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system. [Curr Opin Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSYork Researcher Awarded £1.2 Million for New Blood Cancer Research A University of York scientist has been granted significant new funding from Cancer Research UK to carry out research into a specific kind of blood cancer. Dr. Ian Hitchcock, Lecturer in Biomedical Sciences in York’s Department of Biology, will investigate myeloproliferative neoplasms. [University of York] Press Release BioSight, Ltd announced completion of last patient treatment in its extended Phase I/II clinical study of BST-236 in acute leukemia patients. The Phase I/II clinical trial is a dose-escalation open-label single arm study to evaluate the safety and efficacy of BST-236 as a single agent in adults with acute myeloid leukemia or acute lymphoblastic leukemia. [BioSight, Ltd (PR Newswire Association LLC.)] Press Release PharmaMar Starts a Quadruple Combination Study with Aplidin® for the Treatment of Multiple Myeloma PharmaMar announced the start of a multicenter quadruple combination clinical study with Aplidin®, along with other compounds for the treatment of multiple myeloma. [PharmaMar] Press Release H3 Biomedicine Inc. announced that the FDA has granted the company an orphan drug designation for H3B-8800, its lead clinical compound for the treatment of patients with acute myelogenous leukemia and chronic myelomonocytic leukemia. [H3 Biomedicine Inc.] Press Release | |
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POLICY NEWSBudget Cuts Fuel Frustration among Japan’s Academics Japan’s premier scientific research institution, RIKEN, turned 100 this year, and celebrated with a grand ceremony attended by the empress and emperor. But not everybody was in the mood to party. In the old days, RIKEN was known as a paradise for scientists because of its generous funding. No longer: as Japan cuts off funds in the face of continuing financial uncertainty, the cracks are starting to show. [Nature News] Editorial New FDA Security Rules Will Bar Agency from Hiring Some Foreign Nationals The FDA is moving to adopt a new policy on security background checks that is sowing confusion and alarm among some of its scientists. The change, described in a “communications plan” shared with the agency’s senior staff, appears to effectively bar the agency from hiring—as employees or contractors—foreign nationals who have not lived in the United States for a total of three out of the last five years. [ScienceInsider] Editorial Researchers Rally around Science Advocate Convicted in Egypt In a surprising outcome, an Egyptian judge sentenced Ismail Serageldin, founding director of Egypt’s Library of Alexandria, to 3.5 years in prison for financial misdemeanors. Serageldin has appealed the verdict, and more than 180 scientists, engineers, physicians, and public figures issued a declaration of support (in Arabic) on his behalf. [ScienceInsider] Editorial US Biomedical-Research Facilities Unprepared for Attacks and Natural Disasters Science panel says institutions need to do more to prevent and mitigate damage to research equipment and animals. [Nature News] Editorial
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EVENTSNEW Regenerative Biology and Applications: Cell Differentiation, Tissue Organization and Biomedical Engineering NEW Towards Transformative Therapies for Sickle Cell Disease Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Production Manager – Blood and Related Transfusion Products (Blood Systems Research Institute) Research Assistant – Myeloid Neoplasias (University of Oxford) Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) Postdoctoral Fellow – Regenerative Medicine (Loma Linda University) Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami) PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) 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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