Hematopoiesis News 7.46 November 22, 2016 | |
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TOP STORYEpigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells To define the extent of—and molecular basis for—heterogeneity, the authors overlaid functional, transcriptional, and epigenetic attributes of hematopoietic stem cells (HSCs) at a clonal level using endogenous fluorescent tagging. Endogenous HSC had clone-specific functional attributes over time in vivo. [Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Clonal Fate Mapping Quantifies the Number of Hematopoietic Stem Cells that Arise during Development Scientists applied single-cell and clonal analysis of hematopoietic stem cells (HSCs) in zebrafish to quantify developing HSCs. Targeting creERT2 in developing cd41:eGFP+ HSCs enabled long-term assessment of their blood contribution. [Nat Cell Biol] Abstract Inactivation of KLF4 Promotes T Cell Acute Lymphoblastic Leukemia and Activates the MAP2K7 Pathway Researchers showed that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T cell acute lymphoblastic leukemia (T-ALL). In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells. [Leukemia] Full Article The authors investigated the clonal architecture of the CD34+CD38– hematopoietic stem/progenitor cell compartment and interrogated dominant clones for myelodysplastic syndromes-initiating cells. They found that clones mainly accumulate mutations in a linear succession with retention of a dominant subclone. [Blood] Abstract Reprogramming Mouse Fibroblasts into Engraftable Myeloerythroid and Lymphoid Progenitors Investigators showed that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into ‘induced hematopoietic progenitors’ (iHPs). Functionally, iHPs generate acetylcholinesterase+ megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to four months in vivo. [Nat Commun] Full Article The receptor tyrosine kinase Axl can mediate survival and therapy resistance of different cancer cells. Researchers investigated the therapeutic potential of Axl inhibition in chronic myeloid leukemia. [Clin Cancer Res] Abstract Researchers identify that Smac mimetics such as BV6, which antagonizes Inhibitor of Apoptosis proteins, elicit necroptosis in acute myeloid leukemia cells, in which apoptosis is inhibited pharmacologically by caspase inhibitors or genetically by caspase-8 knockdown. [Oncogene] Abstract Scientists identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells. Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. [Cell Rep] Full Article | Graphical Abstract The authors investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow cellularity was restored through enhanced proliferation of the stem cells. [Sci Rep] Full Article CLINICAL RESEARCHPhiladelphia chromosome (Ph) –like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. Investigators sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. [J Clin Oncol] Abstract | Press Release | Full Article Impact of Graft-versus-Host Disease on Outcomes after Unrelated Cord Blood Transplantation Investigators analyzed the impact of acute and chronic graft-versus-host disease (GVHD) on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first unrelated cord blood transplantation. The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. [Leukemia] Abstract Little is known about the distribution and clonality of the TRDV repertoire in T cell receptor (TCR) of γδ T cells and their effects on the clinical outcome of patients with acute myeloid leukemia (AML). The authors aimed to assess whether the oligoclonal expansion of TCR Vδ T cells could be used as an immune biomarker for AML outcome. [J Hematol Oncol] Full Article | |
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REVIEWSGenetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSCTI BioPharma Corp. announced that data from the randomized Phase III PERSIST-2 clinical trial comparing the investigational agent pacritinib, an oral multikinase inhibitor, with physician-specified best available therapy, including ruxolitinib, for treatment of patients with myelofibrosis whose baseline platelet counts are less than 100,000 per microliter will be presented in a late-breaking oral presentation. [Press release from CTI BioPharma Corp. discussing research to be presented at 58th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release Opsona Therapeutics Ltd. announced that it will present preliminary results from its ongoing prospective, open label Phase I/II study being conducted with OPN-305 in second-line lower risk MDS. [Press release from Opsona Therapeutics Ltd. discussing research presented at 58th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release | |
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INDUSTRY NEWSGilead Sciences, Inc. announced top-line results from two Phase III clinical trials (SIMPLIFY 1 and 2) evaluating momelotinib, an investigational inhibitor of Janus kinase compared to ruxolitinib or best alternative therapy in patients with myelofibrosis. The SIMPLIFY-1 study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for splenic response rate at week 24, defined as the percentage of patients experiencing a ≥ 35 percent reduction in spleen volume. [Gilead Sciences, Inc.] Press Release Janssen Biotech, Inc. announced the U.S. Food and Drug Administration (FDA) has approved DARZALEX® in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. [Janssen Biotech, Inc.] Press Release Novartis announced it has acquired Selexys Pharmaceuticals Corporation, a company specializing in development of therapeutics in certain hematologic and inflammatory disorders. Novartis exercised its right to acquire Selexys following receipt of results of the SUSTAIN study, a Phase II trial evaluating the use of SelG1, an anti-P-selectin antibody, in the reduction of vaso-occlusive pain crises in patients with SCD. [Novartis] Press Release Teva Pharmaceutical Industries Ltd. announced it has obtained approval from the European Commission for an indication extension of Trisenox® (arsenic trioxide). This marks an important advancement in treatment for APL patients in Europe, as it is the first time that a form of acute leukemia can be effectively treated with a regimen that is entirely chemotherapy-free. [Teva Pharmaceutical Industries Ltd.] Press Release | |
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POLICY NEWSCanadian Researcher in Legal Battle to Keep Her Interviews Confidential When Canadian graduate student Marie-Ève Maillé held interviews with 93 people in 2010 about a massive wind farm being built in the Arthabaska region of Quebec, she made a promise that social scientists routinely make: that her respondents would remain anonymous, and that nobody would be able to trace quotes in her thesis back to them. [ScienceInsider] Editorial Cautious Welcome for UK’s Vague £2 Billion Research Pledge UK scientists have welcomed a surprise government promise to invest an extra £2 billion (US$2.5 billion) per year into research and development by 2020 – although details of the pledge will not be made clear for at least another two days. [Nature News] Editorial Conservatives, Liberals Team Up against Animal Research “Painful, bizarre, and wasteful experiments.” Buying dogs “just to cut them apart … and kill them.” These statements might sound like the rhetoric used by extreme animal rights groups, but they come from White Coat Waste—a new, unlikely coalition of fiscal conservatives and liberal activists that aims to end federal funding for research involving dogs and other animals by targeting people’s pocketbooks in addition to their heartstrings. [ScienceInsider] Editorial
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EVENTSNEW Cellular Therapy 2017 International Symposium Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) NEW Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Postdoctoral Fellowship – Stem Cell and Red Cell Biology (Lund University) Postdoctoral Fellow(s) – Various Projects (Cincinnati Children’s Hospital Medical Center) Postdoctoral Fellow – Stem Cell Biology and Hematology (Center for Cell-Based Therapy) Postdoctoral Fellowship – Proteomic Hematology (Lund University) Postdoctoral Fellow – Proteomic Hematology (Lund University) Full Member Faculty Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Research Associate – Hematology (Editas Medicine) Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation) Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes) 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 7.46 | Nov 22 2016