Hematopoiesis News 9.45 November 13, 2018 | |
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TOP STORYGenetic deletion of Jarid2 either reduced overall survival of animals with myeloproliferative neoplasms or drove transformation to secondary acute myeloid leukemia, depending on the timing and context of co-operating mutations. Mechanistically, JARID2 recruited PRC2 to epigenetically repress self-renewal pathways in hematopoietic progenitor cells. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis Chromatin assembly factor (CAF)B1 had a pro-leukemia effect by binding chromatin at discrete sites and interfering with occupancy of transcription factors that promote myeloid differentiation, such as CEBPA. Reducing Chaf1b activity by either heterozygous deletion or overexpression of a CAF1 dominant negative allele was sufficient to suppress leukemogenesis in vivo without impairing normal hematopoiesis. [Cancer Cell] Abstract | Graphical Abstract Researchers showed that HSCs harbor an early, constitutively active innate immune block to lentiviral transduction that can be efficiently overcome by cyclosporine H (CsH). CsH potently enhanced gene transfer and editing in human long-term repopulating HSCs by inhibiting interferon-induced transmembrane protein 3, which potently restricts VSV glycoprotein-mediated vector entry. [Cell Stem Cell] Full Article | Graphical Abstract Scientists demonstrated that dysregulated necroptosis in hematopoiesis promotes bone marrow progenitor cell death that incites inflammation, impairs HSCs, and recapitulates the salient features of the bone marrow failure disorder, myelodysplastic syndrome. [Blood] Abstract By taking advantage of knockout mouse models, investigators demonstrated that increased Cdc42 activity levels correlate with the repression of the nuclear envelope protein LaminA/C, which controls chromosome 11 distribution, H4K16ac polarity, and nuclear volume and shape in aged HSCs. [Genome Biol] Full Article Loss of the BCR-FGFR1 GEF Domain Suppresses RHOA Activation and Enhances B-Lymphomagenesis in Mice Deletion of guanidine nucleotide exchange factor (GEF) domain increased leukemogenesis, enhanced cell survival and proliferation, and promoted stem cell expansion and lymph node metastasis. [Cancer Res] Abstract Scientists showed that thrombopoietin rapidly upregulates mitochondrial activity in HSCs, an activity accompanied by differentiation to a megakaryocyte (Mk) lineage. Moreover, in unperturbed hematopoiesis, HSCs with high mitochondrial activity exhibited Mk-lineage differentiation in vitro and myeloid lineage-biased reconstitution in vivo. [Cell Rep] Full Article | Graphical Abstract Researchers developed a nonviral system based on megakaryocytic microparticles for targeted delivery of plasmid DNA and small RNAs to hematopoietic stem and progenitor cells. [Sci Adv] Full Article CLINICAL RESEARCHRole of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation The authors comprehensively investigated how donor clonal hematopoiesis of indeterminate potential affects outcome of allogeneic HSC transplantation. [J Clin Oncol] Abstract Safety and efficacy of autologous HSC transplantation performed following natalizumab discontinuation was retrospectively compared with conventional disease‐modifying treatments. [Eur J Neurol] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSClonal Hematopoiesis: Genes and Underlying Mechanisms in Cardiovascular Disease Development The clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and HSCs can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease through acquired mutations in genes. [J Cell Physiol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSTG Therapeutics, Inc. announced the first company sponsored Phase I study of its novel, orally available and covalently-bound Bruton Tyrosine Kinase (BTK) inhibitor, TG-1701, is open for enrollment for patients with relapsed or refractory B-cell malignancies. [TG Therapeutics, Inc.] Press Release BeiGene, Ltd. announced the first patient was dosed in a global Phase III clinical trial of its investigational BTK inhibitor zanubrutinib compared with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. [BeiGene, Ltd.] Press Release Bristol-Myers Squibb Company announced that the FDA approved Empliciti injection for intravenous use in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. [Bristol-Myers Squibb Company] Press Release Modus Therapeutics Announces FDA Acceptance of Sevuparin IND for Treatment of Sickle Cell Disease Modus Therapeutics AB announced that the FDA has accepted its sevuparin IND for the treatment of sickle cell disease. [Modus Therapeutics AB] Press Release | |
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POLICY NEWSChina’s Crackdown on Genetics Breaches Could Deter Data Sharing China’s enormous population is a genetics goldmine. But the government, wary that this data could be exploited for profit, has been cracking down on researchers and companies that violate rules on sharing its citizens’ genetic material and information. [Nature News] Editorial Be Open about Drug Failures to Speed Up Research Access to evidence from disappointing drug-development programs advances the whole scientific process, explain Enrica Alteri and Lorenzo Guizzaro. [Nature News] Editorial How Facebook and Twitter Could Be the Next Disruptive Force in Clinical Trials Participants in medical research are more empowered than ever to influence the design and outcomes of experiments. Now, researchers are trying to keep up. [Nature News] Editorial More Researchers Denied UK Entry to Attend Meetings A number of researchers seeking to attend scientific and medical meetings in the UK in recent weeks have had their visa applications denied by the British government. [The Scientist] Editorial
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EVENTSNEW Cell Symposia: Translation of Stem Cells to the Clinic: Challenges and Opportunities Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Staff Scientist – Hematology (St. Jude Children’s Research Hospital) Assistant Project Scientist – Hematology and Oncology (University of California, Davis) Postdoctoral Scientist – Hematology (University Medical Center Freiburg) Research Scientist – Hematological Malignancies (MD Anderson Cancer Center) Postdoctoral Position – Gene Modification in HSCs (University of Wisconsin-Madison) Faculty Positions – Hematology and Oncology (UC Davis) Postdoctoral Position or PhD Student – Bioinformatics in Leukemia (RWTH Aachen Medical School) Postdoctoral Associate – Hematopoiesis and Leukemia (The Jackson Laboratory) 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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