Hematopoiesis News 9.23 June 12, 2018 | |
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TOP STORYMetformin Induces FOXO3-Dependent Fetal Hemoglobin Production in Human Primary Erythroid Cells Whole exome sequence analysis of rare genetic variants in sickle cell disease patients identified FOXO3 as a candidate regulator of red blood cell fetal hemoglobin. Researchers validated these genomic findings through loss and gain of function studies in normal human CD34+ hematopoietic stem and progenitor cells induced to undergo erythroid differentiation. [Blood] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists showed here that fPrdm16 was critical for HSC maintenance, induced multiple genes involved in GTPase signaling and repressed inflammation, while sPrdm16 supported B-cell development biased towards marginal zone B-cells and induced an inflammatory signature. [J Clin Invest] Abstract | Full Article Drug Targeting of NR4A Nuclear Receptors for Treatment of Acute Myeloid Leukemia The authors showed that NR4A silencing in acute myeloid leukemia occurs through blockade of transcriptional elongation rather than epigenetic promoter silencing. [Leukemia] Abstract In Vitro Biomimetic Engineering of a Human Hematopoietic Niche with Functional Properties Researchers developed a 3D engineered human bone marrow (BM) analog by recapitulating some of the hematopoietic niche elements. This included a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited compositional and structural features of human BM while supporting the maintenance of hematopoietic stem and progenitor cells. [Proc Natl Acad Sci USA] Abstract | Press Release Scientists showed that chemical inhibition of the NF-κB signaling pathway leads to a significant improvement of HSC function from ex vivo cultured human umbilical cord blood derived CD34+ cells. [Haematologica] Abstract | Full Article Investigators showed that Zfp90 was highly expressed in HSCs. Zfp90 deficiency in the hematopoietic system caused impaired HSPC pools and led to HSC dysfunction. They showed that Zfp90 deletion inhibited HSC proliferation, while HSC apoptosis was not affected. [Cell Death Dis] Full Article Wild-Type Kras Expands and Exhausts Hematopoietic Stem Cells Scientists utilized a codon-optimized version of the murine Kras gene (Krasex3op) that they developed, in which silent mutations in exon 3 render the encoded mRNA more efficiently translated, leading to increased protein expression without disruption to the normal gene architecture. They found that Kras protein levels were significantly increased in bone marrow HSCs in Krasex3op/ex3op mice, demonstrating that the translation of Kras in HSCs is normally constrained by rare codons. [JCI Insight] Full Article CLINICAL RESEARCHA randomized, multicenter, open-label study explored the effect of a fixed-dose (FD) of plerixafor versus the approved weight-based (WB) dose for the mobilization of HSCs in patients with non-Hodgkin’s lymphoma and a body weight of ≤70 kg. Exposure to plerixafor was greater in the FD arm relative to the WB arm; however, there was no appreciable difference regarding fold increases of peripheral blood CD34+ cells. [Bone Marrow Transplant] Abstract The Phase III AETHERA trial demonstrated brentuximab vedotin’s efficacy as consolidation therapy in patients with classical Hodgkin lymphoma at high risk of relapse or progression following autologous hematopoietic stem cell transplant. [Biol Blood Marrow Transplant] Abstract | |
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REVIEWSExtravascular Coagulation in Hematopoietic Stem and Progenitor Cell Regulation The hemostatic system plays pivotal roles in injury repair, innate immunity and adaptation to inflammatory challenges. The authors review the evidence that these vascular protective mechanisms have non-traditional roles in hematopoietic stem cell maintenance in their physiological bone marrow niches at steady state and under stress. [Blood] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSDaiichi Sankyo Company, Limited announced that topline results from the pivotal QuANTUM-R Phase III study of single agent quizartinib will be presented. [Press release from Daiichi Sankyo Company, Limited (PR Newswire Association LLC.) discussing research to be presented at the 23rd Congress of the European Hematology Association (EHA), Stockholm] Press Release Nordic Nanovector ASA announced that a poster reporting the ability of Betalutin® to reverse resistance to anti-CD20 treatment in non-Hodgkin’s lymphoma cell lines will be presented. [Press release from Nordic Nanovector ASA discussing research to be presented at the 2018 American Association for Cancer Research (AACR) International Meeting: Advances in Malignant Lymphoma, Boston] Press Release | |
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INDUSTRY NEWSMaxCyte, Inc. announced it has entered into a Cooperative Research and Development Agreement with the U.S. National Institutes of Health (NIH). Under this new agreement, MaxCyte and the National Heart, Lung, and Blood Institute, part of the NIH, will aim to develop treatments for individuals with sickle cell disease using next-generation CRISPR/Cas9-based single-nucleotide correction enabled by MaxCyte’s cell engineering platform. [MaxCyte, Inc.] Press Release GT Biopharma, Inc. announced preliminary clinical data taken from an interim review, or snapshot, of the OXS-1550 Phase I/II trial following a Bi-Specific Antibody Drug Conjugate Advisory Board meeting and follow up discussions. [GT Biopharma, Inc.] Press Release Amgen announced that the FDA has approved the supplemental New Drug Application to add the positive overall survival data from the Phase III ASPIRE trial to the U.S. Prescribing Information for KYPROLIS®. [Amgen] Press Release Ironwood Pharmaceuticals, Inc. announced that the FDA has granted Orphan Drug Designation to olinciguat for the treatment of patients with sickle cell disease. Olinciguat is an orally administered soluble guanylate cyclase stimulator. [Ironwood Pharmaceuticals, Inc.] Press Release Genentech announced that the FDA has approved Venclexta® in combination with Rituxan® for the treatment of people with chronic lymphocytic leukemia or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. [Genentech] Press Release Nohla Therapeutics announced the European Medicines Agency (EMA) has granted dilanubicel PRIority MEdicines (PRIME) designation for the treatment of patients receiving a Hematopoietic Stem Cell Transplant. [Nohla Therapeutics] Press Release | |
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POLICY NEWSChina Introduces Sweeping Reforms to Crack Down on Academic Misconduct China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial More Restrictive U.S. Policy on Chinese Graduate Student Visas Raises Alarm Reversing yet another policy of the previous administration, the U.S. Department of State began applying tougher restrictions on some Chinese graduate students. The new policy shortens from five years to one year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. [ScienceInsider] Editorial Leading Salk Scientist Resigns after Allegations of Harassment The prominent cancer biologist Inder Verma unconditionally resigned from the Salk Institute for Biological Studies in San Diego, California, June 6, and the research institute’s board of trustees voted unanimously to accept his resignation. [ScienceInsider] Editorial Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study Sexual harassment is pervasive throughout academic science in the United States, driving talented researchers out of the field and harming others’ careers, finds a report from the US National Academies of Sciences, Engineering, and Medicine in Washington DC. The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial North American Universities Increasingly Cancel Publisher Packages Florida State University (FSU) will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. Back in April, FSU announced that it would not renew a so-called “big deal” with Elsevier in 2019, due to its “high and ever-increasing cost,” and would instead subscribe to a subset of the most-needed journals. The university’s move represents the latest example of academic libraries walking away from these comprehensive and expensive subscriptions, which include all or most of a publisher’s catalog, and instead signing up for a la carte titles. [The Scientist] Editorial
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EVENTSNEW American Society of Hematology (ASH) Meeting on Lymphoma Biology Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Leukemogenesis (Erasmus Medical Center Cancer Institute) NEW Postdoctoral Scientist – Stem Cell Biology (University of Oxford) Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine) Cancer Researchers – Hematologic Malignancy (Cedars-Sinai Medical Center) Postdoctoral Fellow – Hematopoiesis and Leukemia (University of Pennsylvania) Group Leader – Leukemia Research (Hospital del Mar Research Institute) Postdoctoral Position – Stem Cell and Cancer Research (Institute for Research in Biomedicine) Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine) Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia) 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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