Hematopoiesis News 7.37 September 20, 2016 | |
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TOP STORYUsing a conditional HoxA9 model system, researchers performed a high-throughput phenotypic screen and defined compounds that overcame myeloid differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase enables myeloid differentiation in human and mouse acute myeloid leukemia models. [Cell] Abstract | Press Release | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Targeting Methyltransferase PRMT5 Eliminates Leukemia Stem Cells in Chronic Myelogenous Leukemia Investigators discovered a positive feedback loop between BCR-ABL and protein arginine methyltransferase 5 (PRMT5) in chronic myelogenous leukemia (CML) cells. Overexpression of PRMT5 was observed in human CML leukemia stem cells (LSCs). Silencing PRMT5 with shRNA or blocking PRMT5 methyltransferase activity with the small-molecule inhibitor PJ-68 reduced survival, serial replating capacity, and long-term culture-initiating cells in LSCs from CML patients. [J Clin Invest] Full Article The Oncometabolite 2-Hydroxyglutarate Activates the mTOR Signaling Pathway In gliomas and acute myeloid leukaemias, isocitrate dehydrogenases 1 and 2 (IDH1/2) mutations confer gain-of-function leading to production of the oncometabolite R-2-hydroxyglutarate (2HG) from α-ketoglutarate (αKG). The authors showed that generation of 2HG by mutated IDH1/2 leads to the activation of mTOR by inhibiting KDM4A, an αKG-dependent enzyme of the Jumonji family of lysine demethylases. [Nat Commun] Full Article | Press Release Evi1 Regulates Notch Activation to Induce Zebrafish Hematopoietic Stem Cell Emergence The authors identified the zebrafish transcriptional regulator evi1 as critically required for Notch-mediated endothelial-to-hematopoietic transition. In vivo live imaging studies indicated that evi1 suppression impairs endothelial cells progression to hematopoietic fate and therefore hematopoietic stem cells emergence. [EMBO J] Abstract | Graphical Abstract Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-Like Phenotype Scientists demonstrated that B cell CLL/lymphoma 11A (BCL11A) is indispensable for normal hematopoietic stem cell (HSC) function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. They found that downregulation of cyclin-dependent kinase 6, and the ensuing cell-cycle delay, correlate with HSC dysfunction. [Cell Rep] Full Article | Graphical Abstract Investigators found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AMLMLL cells. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AMLMLL and in xenografts of a human AML-MLL cell line. [Sci Signal] Abstract | Press Release To identify a molecular pathway capable of cooperating with PTEN deficiency to drive oncogenic transformation of leukocytes, researchers performed an unbiased transformation screen with a library of tyrosine kinases. They found that activation of NTRK2 is able to confer a full growth phenotype of Ba/F3 cells in an IL3-independent manner in the PTEN-null setting. [Cell Discov] Full Article CLINICAL RESEARCHScientists analyzed 192 consecutive patients with de novo acute myeloid leukemia (AML) aged ≥60 years who were treated with intensive chemotherapy. [Am J Hematol] Abstract Investigators conducted a retrospective analysis to compare outcomes in adult patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation with cyclophosphamide in combination with total body irradiation (TBI), oral busulfan, or intravenous busulfan conditioning regimens. [Biol Blood Marrow Transplant] Abstract Investigators present the outcome of 26 children who developed cyclosporine A-neurotoxicity following allogeneic hematopoietic stem cell transplantation [Bone Marrow Transplantation] Full Article In a two-center safety surveillance study, 245 healthy volunteer stem cell donors were enrolled. Of 244 donors who began mobilization with twice-daily Sandoz biosimilar filgrastim, 242 received a full or partial course of granulocyte-colony-stimulating factors and underwent apheresis. Efficacy and safety were assessed and are reported. [Transfusion] Full Article | |
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REVIEWSThe authors summarize the current understanding of the role of bone Marrow endothelial cells (ECs) and perivascular cells in regulating hematopoietic stem cell (HSC) maintenance and regeneration and highlight the contribution of newly discovered EC-derived paracrine factors that regulate HSC fate. [Stem Cells Transl Med] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSSELLAS Life Sciences Group announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the US National Heart, Lung and Blood Institute, National Institutes of Health. The research plan of the CRADA is designed to develop a novel acute myeloid leukemia minimal residual disease (MRD) assay for monitoring the expression of multiple genes that can document the kinetics of MRD in acute myeloid leukemia during treatment with SELLAS’ most advanced product candidate, galinpepimut-S, the Company’s WT1 cancer vaccine. [SELLAS Life Sciences Group] Press Release Xencor, Inc. announced that the first patient has been dosed in a Phase I clinical trial of XmAb®14045 for the treatment of acute myeloid leukemia and other CD123-expressing hematologic malignancies. [Xencor, Inc.] Press Release | |
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EVENTSNEW Stem Cell Clonality Meeting NEW International Conference on Stem Cell Engineering 2016 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Postdoctoral Fellow – Healthy Ageing of Human Haematopoietic Stem Cells (University of Cambridge) Research Fellow – Cancer Biology (University of Michigan) PhD – Tumor Microenvironment in Leukemia (Georg-Speyer-Haus) Postdoctoral Scholar – Tumor Biology (The Pennsylvania State University College of Medicine) Research Technologist (Pennsylvania State University) Postdoctoral Stipend – Development of Immune System (Lund University) Postdoctoral Research Scientist (National Taiwan University) Postdoctoral Position – Tumor Immunology (Roswell Park Cancer Institute) Postdoctoral Fellow – Hematopoietic Stem Cells (University of Pennsylvania) Assistant Member Faculty – Platinum/Immunotherapy (Fred Hutchinson Cancer Research Center) Cytogenetics Laboratory Supervisor (Fred Hutchinson Cancer Research Center) 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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Home Hematopoiesis News Volume 7.37 | Sep 20 2016