Hematopoiesis News 8.36 September 12, 2017 | |
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TOP STORYm6A Modulates Hematopoietic Stem and Progenitor Cell Specification Investigators showed that N6-methyladenosine (m6A) determines cell fate during the endothelial-to-hematopoietic transition to specify the earliest hematopoietic stem/progenitor cells during zebrafish embryogenesis. They identified that the delayed YTHDF2-mediated mRNA decay of the arterial endothelial genes notch1a and rhoca contributes to this deleterious effect. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists evaluated hematopoiesis in mice heterozygous for a constitutive null Dnmt3a mutation. With no other manipulations, Dnmt3a+/– mice developed myeloid skewing over time, and their hematopoietic stem/progenitor cells exhibited a long-term competitive transplantation advantage. Dnmt3a+/– mice also spontaneously developed transplantable myeloid malignancies after a long latent period, and 3 of 12 tumors tested had cooperating mutations in the Ras/MAPK pathway. [J Clin Invest] Full Article Transient Apoptosis Inhibition in Donor Stem Cells Improves Hematopoietic Stem Cell Transplantation The authors addressed whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. They showed that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. [J Exp Med] Full Article Researchers report that adtrp1 and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. [FASEB J] Abstract Investigators successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. They found that the phenotypically defined long-term-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. [Sci Rep] Full Article Scientists demonstrated that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. Overexpression analysis of RUNX1 showed the RUNX1-binding site-directed DNA demethylation. The RUNX1-mediated DNA demethylation was also observed in DNA replication-arrested cells. [Blood Adv] Full Article | Graphical Abstract CLINICAL RESEARCHThe authors genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E in order to study the effect of HLA-E as NK-alloreactivity mediator on hematopoietic stem cell transplantation (HSCT) outcome in an acute leukemia setting. Analysis of the data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both, univariate and multivariate analyses for five year overall survival. [Haematologica] Full Article Researchers hypothesized that altered soluble interleukin-7 receptor (sIL-7Rα) levels may cause adverse outcomes in patients undergoing hematopoietic stem cell transplantation. They investigated the impact of the IL-7Rα single nucleotide polymorphisms rs6897932, which has been associated with release of IL-7R. [Clin Immunol] Abstract | Graphical Abstract Investigators evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma. Forty-three patients received allo-HCT after the first line of therapy. Non-relapse mortality and relapse/progression incidence at five years were 12% and 65%, respectively. [Bone Marrow Transplant] Abstract | |
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REVIEWSInflammation: A Key Regulator of Hematopoietic Stem Cell Fate in Health and Disease The author details recent advances and unanswered questions at the intersection between inflammation and HSC biology in the contexts of development, aging and hematological malignancy. [Blood] Abstract Single Cell Analysis of Normal and Leukemic Hematopoiesis Scientists summarize how single cell techniques have been applied to the analysis of hematopoietic stem/progenitor cells in normal and malignant hematopoiesis, with a particular focus on recent advances in single-cell genomics, including how these might be utilized for clinical application. [Mol Aspects Med] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSSyros Pharmaceuticals announced that pharmacokinetic (PK) and pharmacodynamic (PD) data from the ongoing Phase II clinical trial of SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), were presented. [Press release from Syros Pharmaceuticals, Inc. discussing research presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release | |
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INDUSTRY NEWSIovance Biotherapeutics, Inc. announced that it has entered into a preclinical research collaboration with The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, focused on tumor-infiltrating lymphocyte, marrow-infiltrating lymphocyte and peripheral blood-associated lymphocyte technologies. [Iovance Biotherapeutics, Inc.] Press Release Bioverativ Inc. and Bicycle Therapeutics Ltd. announced a research collaboration focused on the discovery, development and commercialization of innovative therapies for hemophilia and sickle cell disease. [Bioverativ Inc.] Press Release Leukemia and Lymphoma Society of Canada Awards Record Number of Grants for Blood Cancer Research The Leukemia and Lymphoma Society of Canada awards an unprecedented 41 grants for blood cancer research in Canada this year totaling $3.8 million, setting a new record for the country’s largest voluntary health agency dedicated to blood cancers over its 62-year history. [The Leukemia and Lymphoma Society of Canada (CNW Group Ltd.)] Press Release Hyundai Hope On Wheels® will present The Beckman Research Institute at City of Hope with a $150,000 Hyundai Young Investigator Grant. The grant funds will support the research of principal investigator Dr. Leo David Wang. [Hyundai Hope On Wheels® (PR Newswire Association LLC.)] Press Release Scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at University of California, Los Angeles (UCLA) have initiated a Phase I clinical trial to test a novel cancer treatment for certain kinds of cancers that have a specific tumor marker called NY-ESO-1. Directed by Dr. Antoni Ribas, the trial is the first to genetically engineer blood-forming stem cells to produce cancer-fighting white blood cells called T cells, which constitute part of the immune system. [University of California, Los Angeles] Press Release Global Blood Therapeutics, Inc. announced that the FDA has granted Rare Pediatric Disease designation to GBT440 for the treatment of SCD. GBT440 is being developed as a potentially disease-modifying therapy for SCD. [Global Blood Therapeutics, Inc.] Press Release | |
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POLICY NEWSCongress Rejects Trump Proposals to Cut Health Research Funds Congress has not only rejected the president’s National Institutes of Health proposal; lawmakers from both parties have joined forces to increase spending on biomedical research — and have bragged about it. [The New York Times] Editorial Pall Hangs over U.S.-Iran Science Ties Rising tensions between the U.S. and Iranian governments have frozen most scientific contacts between the two nations, experts reported at a forum. [ScienceInsider] Editorial Senate Panel Seeks Middle Ground on Human Fetal Tissue Research and Abortion A Senate spending panel countered a move by its House of Representatives counterpart to quash federal funding for research that uses human fetal tissue from elective abortions. The move sets up a conflict that will need to be resolved when lawmakers meet later this year to hash out differences between the House and Senate bills, which will provide funding for the National Institutes of Health in the 2018 fiscal year. [ScienceInsider] Editorial South Korean Researchers Lobby Government to Lift Human-Embryo Restrictions More than a decade after a fraud scandal in stem-cell science rocked South Korea, scientists in the field are ramping up pressure on the government to relax the country’s strict regulations on human-embryo research — which many researchers label a ban. [Nature News] Editorial
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EVENTSNEW Keystone Symposia: Emerging Cellular Therapies: T Cells and Beyond Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Opportunities – Biology of Colorectal Cancer (Albert Einstein College of Medicine) NEW Postdoctoral Fellow – Cancer Biology (UCSF Benioff Children’s Hospital) Postdoctoral Position – NK Cell Therapy (Oslo University Hospital) Scientist – Regulators of Hematopoiesis (Università di Roma) Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine) Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre) Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University) 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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