Hematopoiesis News 9.28 July 17, 2018 | |
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TOP STORYA new study has identified some of the first known inherited genetic variants that significantly raise a person’s likelihood of developing clonal hematopoiesis, an age-related white blood cell condition linked with higher risk of certain blood cancers and cardiovascular disease. [Press release from Harvard Medical School discussing online prepublication in Nature] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Clonal Heterogeneity of Acute Myeloid Leukemia Treated with the IDH2 Inhibitor Enasidenib Using sequential patient samples, scientists determined the clonal structure of hematopoietic cell populations at different stages of differentiation. Before therapy, IDH2-mutant clones showed variable differentiation arrest. Enasidenib treatment promoted hematopoietic differentiation from either terminal or ancestral mutant clones; less frequently, treatment promoted differentiation of nonmutant cells. [Nat Med] Abstract Recent advances in single cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. The authors applied such approaches to resolve the molecular mechanisms driving disease in mouse HSCs, using JAK2V617F mutant myeloproliferative neoplasms as a model. [Blood] Abstract Mutant ASXL1 Cooperates with BAP1 to Promote Myeloid Leukemogenesis Researchers report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukemogenesis. BAP1 expression resulted in increased monoubiquitination of ASXL1-MT, which in turn increased the catalytic function of BAP1. [Nat Commun] Full Article Scientists report that specific HDAC5 inhibition highly upregulated CXCR4 surface expression in human cord blood HSCs and progenitor cells (HPCs). This resulted in enhanced SDF-1/CXCR4-mediated chemotaxis and increased homing to the bone marrow environment, with elevated SCID-repopulating cell frequency and enhanced long-term and secondary engraftment in NSG mice. [Nat Commun] Full Article Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment Sub-fractionation of the HSC compartment in retinoic acid (RA)-CFP reporter mice demonstrated that RA-CFP-dim HSCs were largely non-proliferative and displayed superior engraftment potential in comparison with RA-CFP-bright HSCs. [Cell Rep] Full Article | Graphical Abstract Elevated Oxidative Stress Impairs Hematopoietic Progenitor Function in C57BL/6 Substrains Investigators report that C57BL/6J-hematopoietic stem and progenitor cells (HSPCs) display compromised short-term hematopoietic repopulating activity relative to C57BL/6N-HSPCs that is defined by a delay in lymphoid reconstitution and impaired function of specific multi-potent progenitor populations post transplant. [Stem Cell Reports] Full Article Using ex vivo cultures of primary human CD34+ cells as a model, the authors found that mutations in splicing factors SRSF2 and U2AF1 exert distinct effects on proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). SRSF2 mutations caused a dramatic inhibition of proliferation via a G2‐M phase arrest and induction of apoptosis. [Stem Cells] Abstract The Adaptive Remodeling of Stem Cell Niche in Stimulated Bone Marrow Counteracts the Leukemic Niche The stimulation‐induced remodeling of the bone marrow (BM) niche resulted in a positive stimulatory effect on the regeneration of normal HSC, but exerted inhibitory effects on leukemic cells, leading to a competitive advantage for normal HSCs in the BM niche and prolonged survival of mice engrafted with leukemic cells. [Stem Cells] Abstract Investigators studied the dynamic behavior of human HSCs on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. [Sci Rep] Full Article Scientists generated functional CD34 green fluorescent protein reporter human induced pluripotent stem cells, which not only permit label free separation of hematopoietic stem and progenitor cells but also tracing of the emergence and fate of CD34+ progenitors at the single cell level. [Stem Cells Dev] Abstract CLINICAL RESEARCHInvestigators compared overall survival after an allogeneic hematopoietic cell transplant (allo-HCT)2 or donor lymphocyte infusion in relapsed acute myeloid leukemia after a first allo-HCT. [JAMA Oncol] Abstract Outcome of Hematopoietic Stem Cell Transplantation in Dyskeratosis Congenita Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. [Br J Haematol] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSManipulation of Hematopoietic Stem Cell Fate by Small Molecules Compounds The authors present recent progress toward the use of small molecule compounds (SMCs) in hematopoietic stem cell research. They focus on the significant applications of SMCs related to hematopoietic stem/progenitor cell expansion and discuss the associated mechanism. In addition, they give a short summary of the clinical approaches have used the SMCs. [Stem Cells Dev] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSUnum Therapeutics Inc. announced that the company will be presenting pre-clinical data on the use of ACTR T cells in combination with daratumumab, a CD38-specific antibody. [Press release from Unum Therapeutics Inc. discussing research presented at the American Society of Hematology (ASH) Summit on Emerging Immunotherapies for Hematological Diseases, Washington DC] Press Release | |
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INDUSTRY NEWSAbbVie announced it submitted a supplemental New Drug Application to the FDA for venetoclax in combination with a hypomethylating agent or in combination with low-dose cytarabine for the treatment of newly diagnosed patients with acute myeloid leukemia who are ineligible for intensive chemotherapy. [AbbVie] Press Release Gamida Cell, a leading cellular and immune therapeutics company, announced that the FDA has granted orphan drug designation for NiCord as a treatment for hematopoietic stem cell transplantation. [Gamida Cell] Press Release Nohla Therapeutics announced that the FDA has granted Nohla’s lead product candidate, dilanubicel, Orphan Drug Designation for reduction of morbidity and mortality associated with hematopoietic stem cell transplant. [Nohla Therapeutics] Press Release | |
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POLICY NEWSResearchers Celebrate Rejection of Controversial Copyright Policy Early-career researchers are pleased at European leaders’ rejection of a copyright policy that would have introduced restrictions to text-and-data mining of scientific papers. [Chemistry World] Editorial Science Journals End Open-Access Trial with Gates Foundation The publisher of Science ended a pilot partnership that allowed open-access (OA) publishing for researchers funded by the Bill & Melinda Gates Foundation. The trial was an effort to accommodate a policy clash between the Gates Foundation, which has enforced strict OA demands since 2017, and publishers that run subscription journals which don’t comply with those terms. [Nature News] Editorial
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EVENTSNEW The New York Stem Cell Foundation (NYSCF) Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center) Research Technologist – Hematopoietic (STEMCELL Technologies Inc.) Endowed Chair – Cancer Research (University of Iowa Health Care) Investigator Scientist – DNA Repair Pathways (Medical Research Council) Career Development Program – Glycoscience (BloodCenter of Wisconsin) Research Fellow – Stem Cell Biology & Engineering (New York Blood Center) Postdoctoral Researcher – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet) Postdoctoral Fellow – Leukemogenesis (Erasmus Medical Center Cancer Institute) 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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