Hematopoiesis News 8.11 March 21, 2017 | |
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TOP STORYThe authors report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1). Genetic deletion of Fos and Dusp1 suppressed tumor growth in a BCR-ABL fusion protein kinase–induced mouse model of chronic myeloid leukemia. [Nat Med] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Human Hematopoietic Stem Cell Lineage Commitment Is a Continuous Process Scientists integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human hematopoietic stem cells (HSCs) towards lineage commitment. During homeostasis, individual HSCs gradually acquired lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations. Instead, unilineage-restricted cells emerged directly from a ‘continuum of low-primed undifferentiated hematopoietic stem and progenitor cells’. [Nat Cell Biol] Abstract By performing a gene expression profile of NOTCH1 mutated (NOTCH1-mut) versus NOTCH1 wild type chronic lymphocytic leukemia (CLL), researchers identified a gene signature of NOTCH1-mut CLL characterized by upregulation of genes related to ribosome biogenesis, such as nucleophosmin1 and ribosomal proteins. [Leukemia] Abstract Common Nonmutational NOTCH1 Activation in Chronic Lymphocytic Leukemia Investigators report that the active intracellular portion of NOTCH1 (ICN1) is detectable in 50% of peripheral blood chronic lymphocytic leukemia (CLL) cases lacking gene mutations. They identified a “NOTCH1 gene-expression signature” in CLL cells, and showed that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. [Proc Natl Acad Sci USA] Abstract Regulation of NF-κB by PML and PML-RARα Scientists demonstrated that promyelocytic leukemia (PML) promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells showed normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. [Sci Rep] Full Article Zebrafish Caudal Hematopoietic Embryonic Stromal Tissue (CHEST) Cells Support Hematopoiesis Researchers report the generation of CHEST cells from 72-hours post fertilization caudal hematopoietic tissue, the site of embryonic hematopoietic stem and progenitor cells (HSPCs) expansion in fish. Morphological and transcript analysis of these cultures indicates lymphoid, myeloid, and erythroid differentiation, indicating that CHEST cells are a useful tool for identifying molecular signals critical for HSPC proliferation and differentiation in the zebrafish. [Sci Rep] Full Article Investigators established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. [Stem Cell Res Ther] Full Article SB939 is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and scientists investigated if this drug could overcome BCL2-like 11 (BIM) deletion polymorphism-induced tyrosine kinase inhibitor resistance. They found that SB939 corrects BIM pre-mRNA splicing in chronic myeloid leukemia (CML) cells with the BIM deletion polymorphism, and induces apoptotic cell death in CML cell lines and primary cells with the BIM deletion polymorphism. [PLoS One] Full Article CLINICAL RESEARCHThe single-arm, Phase II ENESTfreedom trial assessed the potential for treatment-free remission following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 and greater than or equal to two years of frontline nilotinib therapy were enrolled. [Leukemia] Full Article The authors retrospectively analyzed autologous stem cell transplantation (ASCT)-autologous-non-myeloablative (NMA) allogeneic SCT outcomes of 59 high-risk (HR) and relapsed multiple myeloma (MM) patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk MM upfront ASCT alone were comparable. [Bone Marrow Transplant] Abstract Researchers investigated the efficacy and adverse events of autologous hematopoietic stem cell transplantation in the treatment of children with multiple sclerosis using data from the European Society for Blood and Marrow Transplantation registry. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. [Bone Marrow Transplant] Abstract The authors evaluated the factors contributing to the occurrence of adverse events of cryopreserved hematopoietic progenitor cells collected by apheresis (HPC-A) infusion. Between January 2009 and June 2014, a total of 1269 consecutive HPC-A infusions were given to adult patients undergoing autologous HSC transplantation at Barnes-Jewish Hospital. [Transfusion] Abstract | |
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REVIEWSTregs: Hype or Hope for Allogeneic Hematopoietic Stem Cell Transplantation? The discovery of T regulatory cells (Tregs) has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. [Bone Marrow Transplant] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSERYTECH Presents New Preclinical Anti-Tumor Data on Erymethionase ERYTECH Pharma announced the presentation of new anti-tumor data supporting the company’s preclinical product erymethionase. Results from the preclinical study demonstrate that erymethionase, methionine gamma-lyase-encapsulated in red blood cells using ERYTECH’s proprietary encapsulation platform technology, represents a promising new treatment approach against a broad range of cancers that rely on methionine metabolism. [Press release from ERYTECH Pharma discussing research presented at the American Association for Cancer Research (AACR), Annual Meeting, Washington, D.C.] Press Release | |
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INDUSTRY NEWSBioLineRx Ltd. reported partial results data from its open-label Phase II trial for BL-8040 as a novel monotherapy approach for the mobilization and collection of blood forming stem and progenitor cells from the peripheral blood. [BioLineRx Ltd.] Press Release Fate Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug application for FATE-NK100, the company’s first-in-class adaptive memory natural killer cell product candidate. The company expects a first-in-human clinical trial of FATE-NK100 for advanced acute myeloid leukemia to open enrollment at the Masonic Cancer Center, University of Minnesota following approval of the center’s institutional review board. [Fate Therapeutics, Inc.] Press Release Trovagene and Nerviano Announce License Agreement for Therapeutic Candidate PCM-075 Trovagene, Inc. and Nerviano Medical Sciences, S.r.l. announced that they have signed a license agreement that grants Trovagene exclusive global development and commercialization rights to NMS-1286937, which Trovagene refers to as PCM-075. [Trovagene, Inc.] Press Release Stem Cell, Regenerative Medicine Leaders Join Forces to Advance Canada’s Position in the Field Stem cell science belongs to Canada and it is powering regenerative medicine. Leaders from across this emerging sector have joined forces to advance the field, through the newly created Regenerative Medicine Alliance of Canada. [University of Toronto] Press Release | |
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POLICY NEWSEthical Guidelines on Lab-Grown Embryos Beg for Revamping, Scientists Say Researchers in the U.K. and U.S. recently succeeded for the first time in growing embryos in the lab for nearly two weeks before terminating them, showing that the so-called 14-day rule is no longer a scientific limitation — although it remains a cultural one. Now, a group of Harvard University scientists has published a paper arguing that it is time to reconsider the 14-day rule because of advances in synthetic biology. [Scientific American] Editorial Jailed Iranian Researcher’s Health Worsening Rapidly An Iranian researcher jailed in Tehran for the last 11 months is in declining health after spending more than two months on hunger strike. This month, researchers around the world made urgent appeals for his release. [Nature News] Editorial Trump’s NIH Budget May Include Reducing Overhead Payments to Universities The Trump administration may be planning to help pay for a massive 18% cut to the National Institutes of Health (NIH) by slashing payments to universities and research institutes for overhead costs, ScienceInsider has learned. [ScienceInsider] Editorial
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EVENTSNEW Cell Culture World Congress NEW Mouse Development, Stem Cells & Cancer Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University) Principal Scientist – Immuno Oncology (Celgene Corporation) Postdoctoral Position – Hematopoietic Stem Cell Biology (Inserm) Postdoctoral Fellow – Stem Cell and Leukemia Program (City of Hope) Postdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine) Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation) Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation) Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute) Principal Scientist – Translational Development (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC) 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 8.11 | Mar 21 2017