Hematopoiesis News 10.22 June 11, 2019 | |
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TOP STORYHarnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro Scientists discovered that culturing of HSCs in low calcium increased their maintenance as determined by phenotype, function, and single-cell expression signature. Low-calcium conditions inhibited calpain proteases, which targeted ten-eleven translocated (TET) enzymes, of which TET2 was required for the effect of low calcium conditions on HSC maintenance in vitro. [Cell Stem Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Non-Oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis Investigators showed that diffuse large B cell lymphomas were dependent on mitochondrial lysine deacetylase SIRT3 for proliferation, survival, self-renewal, and tumor growth in vivo regardless of disease subtype and genetics. SIRT3 knockout attenuated B cell lymphomagenesis in VavP-Bcl2 mice without affecting normal germinal center formation. [Cancer Cell] Abstract | Graphical Abstract SIRT1 Regulates Metabolism and Leukemogenic Potential in CML Stem Cells Researchers identified a previously unrecognized role for sirtuin 1 (SIRT1) in mediating increased mitochondrial oxidative phosphorylation in chronic myeloid leukemia (CML) leukemia stem cells. They showed that mitochondrial alterations were kinase independent and that tyrosine kinase inhibitor treatment enhanced inhibition of CML hematopoiesis in SIRT1-deleted mice. [J Clin Invest] Full Article | Press Release | Graphical Abstract Knockdown studies revealed human hematopoietic stem and progenitor cells to be strongly influenced by RUNX3 levels, with modest deficiencies abrogating erythroid differentiation at multiple steps while retaining capacity for granulopoiesis. Transcriptome profiling indicated control by RUNX3 of key erythroid transcription factors, including KLF1 and GATA1. [Haematologica] Abstract Latexin Regulation by HMGB2 Is Required for Hematopoietic Stem Cell Maintenance High-mobility group protein B2 knockdown increased latexin expression at transcript and protein levels, and decreased HSC number and regeneration capacity in vivo. Concomitant blockage of latexin activation significantly reversed these phenotypic changes, suggesting that latexin was one of the downstream targets and functional mediators of high-mobility group protein B2. [Haematologica] Abstract Transcriptional States and Chromatin Accessibility Underlying Human Erythropoiesis Researchers applied deep transcriptomic and accessible chromatin profiling to characterize a faithful ex vivo human erythroid differentiation system from hematopoietic stem and progenitor cells. They revealed stage-specific transcriptional states and chromatin accessibility during various stages of erythropoiesis, including 14,260 differentially expressed genes and 63,659 variably accessible chromatin peaks. [Cell Rep] Full Article | Graphical Abstract GATA2 promoted expansion of hemogenic precursors via the endothelial-to-hematopoietic transition and then helped to maintain hematopoietic stem (HS)-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that human pluripotent stem cell-derived HS-like cells were very similar to human fetal liver-derived HSCs. [Stem Cell Reports] Full Article | Graphical Abstract The authors directly compared the relative efficiency of co-delivery of a novel CRISPR/Cas9 ribonucleoprotein targeting HBB in association with recombinant adeno-associated virus 6 vs. single-stranded oligodeoxynucleotides to introduce the sickle mutation or a silent change in human CD34+ mobilized peripheral blood stem cells derived from healthy donors. [Mol Ther Nucleic Acids] Abstract | Full Article CLINICAL RESEARCHInvestigators characterized the role of CALCRL in acute myeloid leukemia (AML). They analyzed CALCRL expression in collectively more than 1500 well-characterized AML patients from five international cohorts and evaluated associations with survival. [Leukemia] Abstract Scientists evaluated outcomes of T cell receptor α+β+/CD19+-depleted haploidentical HSC transplantation (HSCT) in pediatric patients with primary immune deficiency at a single center in Australia. They evaluated immune reconstitution, looking at time to T cell and B cell reconstitution, and B cell function post-HSCT. Eleven patients with a mean age of 7.92 years were included. [J Clin Immunol] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSSomatic Genetic Rescue in Mendelian Hematopoietic Diseases A growing number of studies of Mendelian hematopoietic disorders indicate that somatic genetic events can offset the pathogenic effect of germline mutations at the cellular level, leading to genetic mosaicism and, in some cases, resulting in a milder disease phenotype. [Nat Rev Genet] Abstract Targeting the Tumor Microenvironment of Leukemia and Lymphoma The authors dissect the stromal compartment in lymphoid organs, focusing on conditions that are prevalent in an autochthonous environment for lymphoid neoplasia. Identification of tumor-promoting factors is instrumental in the selection of therapeutic targets that are part of the immune system. [Trends Cancer] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSJanssen to Present Data from Its Robust Oncology Portfolio and Pipeline Janssen will present 28 company-sponsored abstracts from its leading hematological malignancy portfolio, including the latest results for DARZALEX® and IMBRUVICA®. [Press release from Janssen Global Services, LLC (Business Wire, Inc.) discussing research to be presented at the 24th European Hematology Association (EHA) Annual Congress, Amsterdam] Press Release ArQule to Present Clinical Data for Its BTK Inhibitor, ARQ 531 ArQule, Inc. announced that it will present clinical data from the company-sponsored Phase I dose escalation study on its BTK inhibitor, ARQ 531, for the treatment of relapsed or refractory B-cell lymphoid malignancies in a poster presentation. [Press release from ArQule, Inc. discussing research to be presented at the 24th European Hematology Association (EHA) Annual Congress, Amsterdam] Press Release Onconova Therapeutics Announces Presentations Onconova Therapeutics, Inc. announced two presentations. Dr. Steven Fruchtman, President & CEO, Dr. Ric Woodman, CMO, and Dr. Ronnee Adesanya, VP Medical Affairs, will be attending the conference. [Press release from Onconova Therapeutics, Inc. discussing research to be presented at the 24th European Hematology Association (EHA) Annual Congress, Amsterdam] Press Release Achillion Announces Upcoming Scientific Presentation Achillion Pharmaceuticals, Inc. announced that the final data set for ACH-4471 proof of concept Phase II trial in untreated patients with paroxysmal nocturnal hemoglobinuria was accepted for oral presentation. [Press release from Achillion Pharmaceuticals, Inc. discussing research to be presented at the 24th European Hematology Association (EHA) Annual Congress, Amsterdam] Press Release | |
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INDUSTRY NEWSTaiho Oncology, Inc. announced that it has assumed commercialization responsibility from Otsuka Pharmaceuticals Co., Ltd. for the novel fixed-dose combination of cedazuridine and decitabine and guadecitabine in the US and Canada, subject to regulatory approvals. Taiho Pharma Canada, Inc. will commercialize these compounds in Canada. [Taiho Oncology, Inc.] Press Release Genmab Signs Agreement with Janssen for Next-Generation CD38 Antibody, HexaBody®-CD38 Under the terms of the agreement, Genmab will collaborate exclusively with Janssen on HexaBody-CD38, with Genmab funding research and development activities until completion of clinical proof of concept studies in multiple myeloma and diffuse large B-cell lymphoma. [Genmab A/S] Press Release Astex Pharmaceuticals, Inc. and Otsuka Pharmaceutical Co. Ltd., announced top-line results from the ASCERTAIN Phase III study evaluating cedazuridine and decitabine fixed-dose combination vs decitabine IV in adults with intermediate and high-risk MDS or CMML. [Astex Pharmaceuticals, Inc.] Press Release Innate Pharma Enrolls First Patient in IPH4102 TELLOMAK Phase II Study Innate Pharma SA announced that it has enrolled the first patient in the TELLOMAK Phase II study of IPH4102 in patients with different subtypes of T-cell lymphoma (TCL). IPH4102 is Innate Pharma’s wholly-owned first-in-class anti-KIR3DL2 antibody, developed for the treatment of TCL. [Innate Pharma SA] Press Release Xynomic Dosed First Patient in Phase I/II Lymphoma Trial Xynomic Pharmaceuticals Holdings, Inc. announced that Xynomic has dosed the first patient in a Phase I/II trial that combines abexinostat with ibrutinib in patients with relapsed/refractory mantle cell lymphoma or relapsed/refractory diffuse large B-cell lymphoma at Memorial Sloan Kettering Cancer Center. [Xynomic Pharmaceuticals Holdings, Inc. (GlobeNewswire, Inc.)] Press Release Cellenkos™ announced the initiation of a Phase I Clinical Trial of CK0801, a first-in-class, allogeneic cord blood-derived T-regulatory cell product, for treatment of patients with bone marrow failure syndromes, including aplastic anemia, hypoplastic myelodysplasia, and primary myelofibrosis. [Cellenkos™] Press Release Children’s National Health System announced the opening of a unique chimeric antigen receptor (CAR) T-cell immunotherapy trial for pediatric patients with relapsed positive acute lymphoblastic leukemia. The PLAT-05 trial will focus on targeting the CD19 and CD22 proteins simultaneously found in leukemia cancer cells. [Children’s National Health System (PR Newswire Association LLC.)] Press Release Genentech announced that the FDA has granted accelerated approval to Polivy™ in combination with bendamustine plus Rituxan® for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma, who have received at least two prior therapies. [Genentech, Inc.] Press Release Sierra Announces Momelotinib Granted FDA Fast Track Designation Sierra Oncology, Inc. announced that the FDA has granted Fast Track designation to momelotinib, a JAK1, JAK2 and ACVR1 inhibitor, for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor. [Sierra Oncology, Inc.] Press Release TG Therapeutics, Inc. announced that the company has confirmed its path to submit umbralisib for accelerated approval based on data from the marginal zone lymphoma (MZL) cohort of the UNITY-NHL Phase IIb trial. The company recently had a productive Breakthrough Therapy Designation meeting with the FDA to discuss the MZL submission strategy. [TG Therapeutics, Inc.] Press Release | |
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POLICY NEWSSudanese Academics Defiant as Revolution Turns Bloody Sudan’s universities are shut, flights have been suspended and the Internet remains almost entirely blocked after a brutal crackdown in which paramilitaries are thought to have killed some 100 pro-democracy protestors. But none of this has dented the resolve of the protestors, whose ranks include several prominent academics and whose demands include freeing universities from government influence. [Nature News] Editorial Wellcome Sanger Institute to Close Animal Facility The Wellcome Sanger Institute announced that it would be closing its animal facility, which provides mice, zebrafish, rats, and frogs to geneticists at the institute and internationally, reports Nature. The institute states that the closure is related to the growing use of cell lines and organoids, instead of animals. [The Scientist] Editorial Stem Cell Clinics Co-Opt Clinical-Trials Registry to Market Unproven Therapies, Critics Say On the one hand, the FDA issued a letter stating that what an Arizona distributor was selling as stem cell therapies were “unapproved” and posed “safety concerns.” On the other, a National Institutes of Health database — clinicaltrials.gov — went right on listing the same merchant’s studies, with a link to the company’s website and the word “Recruiting” displayed invitingly in green. [STAT News] Editorial
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EVENTSNEW Keystone Symposia: Tumor Metabolism Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Senior Lecturer Positions – Clinical Oncology or Hematology (Karolinska Institutet) Research Fellow – Hematology, Blood-Disorders & Stem Cell Biology (New York Blood Center) Researcher – Clonal Hematopoiesis & Molecular Epidemiology (Uppsala University) Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Scientist – Hematopoietic Stem Cell Research (DKFZ / HI-STEM) Postdoctoral Scientist – Inflammatory Stress in the Bone Marrow (DKFZ / HI-STEM) Postdoctoral Fellow – Molecular Mechanisms of Myeloma (City of Hope) Assistant Professor – Lymphoma/Myeloma Research (The University of Texas MD Anderson Cancer 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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