Hematopoiesis News 7.44 November 8, 2016 | |
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TOP STORYCRISPR/Cas9 β-Globin Gene Targeting in Human Hematopoietic Stem Cells Scientists present a CRISPR/Cas9 gene-editing system that combines Cas9 ribonucleoproteins and adeno-associated viral vector delivery of a homologous donor to achieve homologous recombination at the β-globin (HBB) gene in hematopoietic stem cells. Notably, they devised an enrichment model to purify a population of hematopoietic stem and progenitor cells with more than 90% targeted integration. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. Researchers undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. [Cancer Cell] Abstract RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML While acquisition of clonal DNA mutations has been linked to increased rates of secondary acute myeloid leukemia (AML) for individuals older than 60 years, the contribution of RNA processing alterations to human hematopoietic stem and progenitor aging and leukemia stem cells (LSCs) generation remains unclear. Comprehensive RNA sequencing and splice-isoform-specific PCR uncovered characteristic RNA splice isoform expression patterns that distinguished normal young and aged human stem and progenitor cells from malignant myelodysplastic syndrome and AML progenitors. [Cell Stem Cell] Abstract | Graphical Abstract Scientists have uncovered a mutually exclusive distribution of EPHB4 receptors in bone marrow sinusoids and ephrin B2 ligands in hematopoietic cells. They determined that signaling interactions between EPHB4 and ephrin B2 control hematopoietic stem and progenitor cells mobilization from the bone marrow. [J Clin Invest] Full Article Expression of the Fetal Hematopoiesis Regulator FEV Indicates Leukemias of Prenatal Origin Scientists identified a transcriptional factor FEV that was expressed in fetal hematopoietic cells and became silent after birth. They characterized that FEV was essential for the self-renewal of hematopoietic stem cells. They next found FEV was expressed in most infant leukemia samples, but not in adult samples, in accord with the known pre-natal origins of the former. [Leukemia] Abstract By using transcription activator-like effect or nucleases (TALEN) technology, researchers created a zebrafish mpl mutant to model human congenital amegakaryocytic thrombocytopenia. Disruption of zebrafish mpl led to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult HSPCs. [Leukemia] Abstract The authors found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor protease-activated receptor-1, in Runx1/Cbfb-deleted MLL-AF9 cells. [Oncogene] Abstract LRBA Is Essential for Allogeneic Responses in Bone Marrow Transplantation Researchers showed that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, they demonstrated that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D. [Sci Rep] Full Article Investigators showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant chronic myeloid leukemia (CML) cells by inducing cell cycle arrest with polyploidy accumulation. [Sci Rep] Full Article CLINICAL RESEARCHThe authors investigated the long-term safety and disease-control data obtained with intravenous busulfan combined with clofarabine in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation. 107 patients with median age 38 years received a matched sibling, or matched unrelated donor transplant for ALL in first complete remission, second complete remission, or more advanced disease. [Biol Blood Marrow Transplant] Abstract Researchers investigated the feasibility and efficacy of intra-bone marrow hematopoietic stem cell transplantation (HSCT) following nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received intra-bone marrow HSCT of either density gradient or buffy coat enriched bone marrow cells. A historical intravenous HSCT cohort served as control. [Biol Blood Marrow Transplant] Abstract | |
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REVIEWSAntigen Receptor Stereotypy in Chronic Lymphocytic Leukemia Stereotypy-based patient classification of chronic lymphocytic leukemia (CLL) has already provided a more compartmentalized view of this otherwise heterogeneous disease and can assist in refining prognostication models. While this is relevant only for the one-third of cases expressing stereotyped BcR IG; in principle, however, the findings from further analysis of the stereotyped subsets may also contribute towards improved understanding of the remaining non-stereotyped fraction of CLL patients. [Leukemia] Abstract Previously a rapidly fatal disease in early childhood, β-thalassemia is now a chronic disease with a greater life expectancy. At present, the only definitive cure is bone marrow transplantation. Therapies undergoing investigation are modulators of erythropoiesis and stem cell gene therapy. [Genet Med] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSBioLineRx Ltd. disclosed positive Phase IIa correlative data, as well as detailed mechanism-of-action data, for BL-8040, the company’s leading oncology platform, that will be presented. [Press release from BioLineRx Ltd. discussing research to be presented at 58th American Society of Hematology (ASH) Annual Meeting and Exhibition, San Diego] Press Release Helsinn and MEI Pharma, Inc. announced that long-term survival and response data from a Phase II clinical study of pracinostat and azacitidine in older patients with acute myeloid leukemia have been selected for oral presentation. [Press release from MEI Pharma, Inc. discussing research to be presented at 58th American Society of Hematology (ASH) Annual Meeting and Exhibition, San Diego] Press Release Jazz Pharmaceuticals to Present New Data Jazz Pharmaceuticals plc announced that eleven abstracts, including four oral presentations, supporting the company’s hematology and oncology portfolio will be presented. [Press release from Jazz Pharmaceuticals plc discussing research to be presented at 58th American Society of Hematology (ASH) Annual Meeting and Exhibition, San Diego] Press Release Kite Pharma, Inc. will show additional detail from the interim analysis from ZUMA-1 as well as new KTE-C19 data and reproducibility in their manufacturing process from their ZUMA-3 and ZUMA-4 trials. The additional data sets continue to provide deeper insights into the therapy’s potential to transform the treatment of B-cell malignancies. [Press release from Kite Pharma, Inc. discussing research to be presented at 58th American Society of Hematology (ASH) Annual Meeting and Exhibition, San Diego] Press Release | |
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INDUSTRY NEWSImago BioSciences announced that the first patients have been dosed in a Phase I/II clinical trial of IMG-7289 for the treatment of high-risk acute myeloid leukemia and high-risk myelodysplastic syndrome. This study will assess the safety, pharmacokinetics, pharmacodynamics and anti-neoplastic activity of IMG-7289, an inhibitor of the epigenetic enzyme lysine-specific demethylase 1. [Imago BioSciences (PR Newswire Association LLC.)] Press Release Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced completion of patient enrollment in the ECHELON-2 clinical trial. ECHELON-2 is a global Phase III randomized trial evaluating ADCETRIS as part of a frontline combination chemotherapy regimen in patients with previously untreated CD30-positive mature T-cell lymphoma (MTCL). ADCETRIS is an antibody-drug conjugate directed to CD30, which is expressed on several types of non-Hodgkin lymphoma, including subsets of MTCL, as well as Hodgkin lymphoma. [Seattle Genetics, Inc.] Press Release | |
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POLICY NEWSHard Work, Little Reward: Nature Readers Reveal Working Hours and Research Challenges A poll answered by thousands of Nature readers suggests that nearly two-thirds have considered quitting research, and that almost 40% work more than 60 hours in a week. The fight for funding is the greatest challenge facing early-career scientists, readers said. [Nature] Editorial Twitterstorm Shows Why Scientific Evidence Matters Grammar and Twitter rarely sit happily, so it would be churlish to point out that when the Welsh MP Glyn Davies tweeted at the weekend: “Nothing more irritating than academics rubbishing the efforts of those operating at the sharp end, without facing up to the hard decisions”, he was inadvertently complaining that people at the sharp end (himself included presumably) do not confront hard decisions. [Nature] Editorial
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EVENTSNEW ASH Annual Meeting & Exposition Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellowship – Proteomic Hematology (Lund University) Therapeutic Development Specialist – Hematology (Celgene Corporation) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Head of Laboratory – Cellular and Molecular Therapies (NHS Blood and Transplant) Postdoctoral Fellow – Proteomic Hematology (Lund University) Lecturer – Cancer Biology (NUI Galway) Full Member Faculty Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Research Associate – Hematology (Editas Medicine) Faculty – Stem Cell Transplantation and Regenerative Medicine (Stanford University Medical School) 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 7.44 | Nov 8 2016