Hematopoiesis News 8.31 August 8, 2017 | |
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TOP STORYUBE2O Remodels the Proteome during Terminal Erythroid Differentiation Scientists identified an anemic mouse line with a null mutation in Ube2o, and used multiplexed quantitative proteomics to identify candidate substrates of UBE2O in an unbiased and global manner. They found that the protein compositions of mutant and wild-type reticulocytes differed markedly. [Science] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)HSC maintenance and lineage differentiation are supported by stromal niches, and the authors found that bone marrow stroma cells are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, they showed that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. [Cell Stem Cell] Abstract | Graphical Abstract Investigators showed that treating mice with estradiol to model estradiol increases during pregnancy induced HSC proliferation in the bone marrow but not HSC mobilization. Treatment with the alternative estrogen receptor α (ERα) ligand 27-hydroxycholesterol induced ERα-dependent HSC mobilization and extramedullary hematopoiesis but not HSC division in the bone marrow. [J Clin Invest] Full Article Samd14-Enh stimulated stem cell factor/c-Kit signaling, which promoted erythrocyte regeneration. Anemia activated Samd14-Enh by induced enhancer components and enhancer chromatin accessibility. Thus, a GATA-2/anemia-regulated enhancer controlled expression of a SAM domain protein that confers survival in anemia. [Dev Cell] Full Article | Press Release | Graphical Abstract Scientists report that both human CD34+CD38– early and CD34+CD38+ intermediate hematopoietic progenitor cells (HPCs) were maintained in the bone marrow (BM) of humanized mice. Chronic human immunodeficiency virus-1 (HIV-1) infection preferentially depleted CD34+CD38– early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected. [PLoS Pathog] Full Article To determine the capacity of stem cells needed to rescue aberrant skeletal development and bone marrow hematopoiesis in vivo, researchers used a skeletal complementation model. Mice deficient in Runx2, a master transcription factor for osteoblastogenesis, failed to form a mineralized skeleton and bone marrow. [Stem Cells] Abstract Investigators report the chemical vapor deposition (CVD) of dual-functional polymer films for the specific and orthogonal immobilization of two biomolecules that govern the fate of hematopoietic stem and progenitor cells. The composition of the CVD polymer and thus the biomolecule ratio were tailored to investigate and optimize the influence of the relative surface concentrations of biomolecules on stem cell behavior. [Biomacromolecules] Abstract The authors established a humanized mouse model by using AF4-mixed-lineage leukemia (MLL) to analyze its transformation potential in human cord blood-derived CD34+ hematopoietic stem/progenitor cells (HSPCs). They showed that AF4-MLL-expressing human CD34+ HSPCs provide enhanced long-term hematopoietic reconstitution in primary immunodeficient recipients but are not endowed with subsequent self-renewal ability upon serial transplantation. [Oncotarget] Full Article As MOG simulated the production of abzymes with high DNase activity, investigators compared the effects of DNA and MOG immunization on experimental autoimmune encephalomyelitis (EAE)-prone mice. In contrast to MOG, immunization with DNA lead to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA, and a reduction in abzyme production. [J Cell Mol Med] Full Article CLINICAL RESEARCHThe authors evaluated the outcomes of haploidentical or mismatched unrelated donor hematopoietic stem cell transplantation after depleting graft versus host disease causing TCRαβCD3+ cells from the graft. At 20.8 months median follow up, 21/25 patients survived and were cured of underlying immunodeficiency. [J Allergy Clin Immunol] Abstract Scientists conducted a retrospective review of a single-institution database including patients with acute myelogenous leukemia who received allogeneic stem cell transplant-hematopoietic stem cell transplantation following conditioning with fludarabine and melphalan (Flu/Mel) or busulfan and cyclophosphamide (Bu/Cy)-based regimens. Patients conditioned with Bu/Cy were significantly younger, but more likely to be treated in an earlier era than those receiving Flu/Mel. [Leuk Lymphoma] Abstract | |
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REVIEWSEpigenetic Dysregulation in Chronic Myeloid Leukemia: A Myriad of Mechanisms and Therapeutic Options The authors review the evidence for subverted epigenetic mechanisms in chronic myeloid leukemia and how these impact on a diverse set of biological pathways, on disease progression, prognosis and drug resistance. [Semin Cancer Biol] Abstract Technical Considerations for the Use of CRISPR/Cas9 in Hematology Research Scientists provide an overview of three recent CRISPR/Cas9 methods in hematology: gene disruption, gene targeting, and saturating mutagenesis. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSX4 Pharmaceuticals Announces Rare Disease Research Collaboration with Yale University X4 Pharmaceuticals announced the initiation of a multi-year sponsored research program with Yale University to develop and study a genetic model of WHIM syndrome, a rare genetic immunodeficiency disease which currently has no approved treatments. [X4 Pharmaceuticals] Press Release Selvita S.A. and The Leukemia & Lymphoma Society announced a partnership to co-fund further preclinical and clinical development of a targeted therapy to treat patients with acute myeloid leukemia (AML). Selvita has discovered and is developing SEL120, a therapy that targets the cyclin-dependent kinase 8 protein, which plays a unique and critical role in gene regulation. [Selvita S.A.] Press Release Helsinn and MEI Pharma, Inc. announced that the first patient has been dosed in the pivotal Phase III study of the investigational agent pracinostat in combination with azacitidine in adults with newly diagnosed acute myeloid leukemia who are unfit to receive intensive induction chemotherapy. [MEI Pharma, Inc.] Press Release Jazz Pharmaceuticals plc announced that the U.S. FDA has approved Vyxeos™ liposome for injection for the treatment of adults with two types of AML, a rapidly progressing and life-threatening blood cancer. Vyxeos is indicated for the treatment of adults with newly-diagnosed t-AML or AML-MRC. [Jazz Pharmaceuticals plc] Press Release | |
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POLICY NEWSFDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby The New York-based doctor who helped a couple have a child using DNA from three people has been told by the U.S. FDA that he can’t go ahead with clinical trials meant to test the technique. [MIT Technology Review] Editorial CRISPR Patent Battle in Europe Takes a ‘Wild’ Twist with Surprising Player MilliporeSigma, a subsidiary of pharmaceutical giant Merck KGaA of Darmstadt, Germany, has become a new major player in the complicated European patent battles over CRISPR, the revolutionary genome-editing tool. [ScienceInsider] Editorial Senate Passes FDA User Fee and Right-to-Try Bills The Senate has voted in quick succession to pass bills reauthorizing the FDA to collect fees from the industry and expanding access to unapproved medicines. President Trump is set to sign the user fee bill into law, while the right-to-try legislation will go to the House. [FierceBiotech] Editorial Discredited Gene-Editing Researcher Vows to Clear His Name A Chinese biologist whose team retracted a high-profile paper on a gene-editing technology has vowed to press ahead with experiments that he hopes will vindicate the potential rival to the CRISPR/Cas9 system. [ScienceInsider] Editorial
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EVENTSNEW American Association of Blood Banks (AABB) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Production Manager – Blood and Related Transfusion Products (Blood Systems Research Institute) Research Assistant – Myeloid Neoplasias (University of Oxford) Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University) Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University) Postdoctoral Fellow – Regenerative Medicine (Loma Linda University) Postdoctoral Fellow – Epigenetics of Hematopoiesis (International Clinical Research Center) Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami) PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center) Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) 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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