Hematopoiesis News 8.05 February 7, 2017 | |
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TOP STORYBy using genome-wide CRISPR-based screens, scientists generated a gene essentiality dataset across 14 human acute myeloid leukemia cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. [Cell] Abstract | Press Release | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The BETi OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of proteolysis-targeting chimera ARV-825 caused sustained and profound depletion of BRD4 and induced significantly more apoptosis in cultured and patient-derived CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. [Leukemia] Abstract Bone Marrow Microenvironment Derived Signals Induce Mcl-1 Dependence in Multiple Myeloma Scientists investigated the role of the bone marrow microenvironment in determining Bcl-2 family dependence in multiple myeloma. They used the Bcl-2/Bcl-xL inhibitor ABT-737 to study the factors regulating whether myeloma is Mcl-1 dependent and thus resistant to ABT-737 induced apoptosis, or Bcl-2/Bcl-xL co-dependent and thus sensitive to ABT-737. [Blood] Abstract In order to examine how reduced PTPROt expression affects chronic lymphocytic leukemia (CLL) in vivo investigators induced CLL in PTPROt-targeted mice. Unexpectedly, loss of both Ptprot alleles delayed disease detection and progression and lengthened survival relative to mice carrying two intact alleles, indicating that PTPROt fulfills a novel tumor-promoting role in CLL. [Oncogene] Abstract Investigators developed a double gene lentiviral vector encoding both human γ-globin and NUP98-HOXA10HD, which was used to transduce human peripheral blood CD34+ cells and increased engraftment 2 to 2.5 fold at 15 weeks post-transplantation in immunodeficient mice. [Mol Ther] Abstract Researchers utilized a mouse model of chronic graft-versus-host disease (cGVHD) to examine whether heavy chain-hyaluronan/pentraxin 3 (HC-HA/PTX3) could attenuate dry eye disease elicited by cGVHD. Their results indicated that subconjunctival and subcutaneous injection of HC-HA/PTX3 preserved tear secretion and conjunctival goblet cell density and mitigated inflammation and scarring of the conjunctiva. [Sci Rep] Full Article The Promotion of Erythropoiesis via the Regulation of Reactive Oxygen Species by Lactic Acid The authors utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of hemoglobin genes and the frequency of GPA+ cells. [Sci Rep] Full Article Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells and leukemia stem cell population. [Biochim Biophys Acta] Abstract NKL Homeobox Gene Activities in Hematopoietic Stem Cells, T-Cell Development and T-Cell Leukemia Researchers analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs and three in common lymphoid progenitors. [PLoS One] Full Article CLINICAL RESEARCHThe authors’ objective was to develop and validate an easy to use myeloma-risk-score (revised Myeloma Comorbidity Index) that allows risk prediction of OS and PFS differences in a large patient cohort. They conducted a geriatric assessment in 801 consecutive myeloma patients, including comorbidity risks obtained at diagnosis. The cohort was examined within a training and validation set. [Haematologica] Abstract | |
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REVIEWSStem and Progenitor Cell Alterations in Myelodysplastic Syndromes Studies have demonstrated that myelodysplastic syndromes (MDS) stem cells are functionally critical for the initiation, transformation and relapse of disease and need to be targeted therapeutically for future curative strategies in MDS. [Blood] Abstract Acute Myeloid Leukemia Targets for Bispecific Antibodies The authors summarize the acute myelogenous leukemia-associated tumor targets and the bispecific antibodies that have been studied. The potentials and limitations of each of these systems are discussed. [Blood Cancer J] Full Article Hematopoietic Stem Cells: Past, Present and Future Human allogeneic stem cell therapy relies on these functional characteristics of hematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimizing risk of graft-versus-host disease developing in the recipient of transplanted stem cells. [Cell Death Discov] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSCellectis has received an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase I clinical trials with UCART123, the company’s most advanced, wholly owned TALEN® gene-edited product candidate, in patients with acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate that the FDA has approved for clinical trials. [Cellectis] Press Release BioMarin Pharmaceutical Inc. announced that the European Medicines Agency (EMA) has granted access to its Priority Medicines (PRIME) regulatory initiative for the company’s investigational gene therapy treatment for severe hemophilia A, BMN 270. [BioMarin Pharmaceutical Inc.] Press Release Ablynx announced that it has submitted a Marketing Authorization Application to the European Medicines Agency for approval of caplacizumab, its first-in-class anti-von Willebrand (vWF) factor Nanobody® for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), an ultra-rare, acute, life-threatening blood clotting disorder with a high unmet medical need. [Ablynx] Press Release Imara Receives Orphan Drug Designation for Lead Product Candidate IMR-687 for Sickle Cell Disease Imara, Inc. announced that the U.S. Food and Drug Administration has granted Orphan Drug designation to the company’s lead product candidate IMR-687 for the treatment of sickle cell disease. [Imara, Inc.] Press Release ARIAD Pharmaceuticals, Inc. announced the submission of a Marketing Authorization Application for its investigational oral anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the European Medicines Agency. ARIAD is seeking marketing approval in the European Union of brigatinib in adult patients with ALK+ non-small cell lung cancer who have been previously treated with crizotinib. [ARIAD Pharmaceuticals, Inc.] Press Release | |
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POLICY NEWSStudy Retraction Reignites Concern over China’s Possible Use of Prisoner Organs A journal has decided to retract a 2016 study because of concerns that its data on the safety of liver transplantation involved organs sourced from executed prisoners in China. The action, taken despite a denial by the study’s authors that such organs were used, comes after clinical ethicist Wendy Rogers of Macquarie University in Sydney, Australia, and colleagues authored a letter to the editor of Liver International, calling for the paper’s retraction in the “absence of credible evidence of ethical sourcing of organs.” [ScienceInsider] Editorial US Government Takes Animal-Welfare Data Offline The US Department of Agriculture agency charged with ensuring the humane treatment of large research animals, such as primates and goats, has quietly scrubbed all inspection reports and enforcement records from its website. The move has drawn criticism from animal-welfare and transparency activists who say the public has the right to know how their tax dollars are being used. [Nature News] Editorial Venezuela Is Running Short on HIV Meds—and Places to Turn for Help On top of its currency being in free fall for three years running, empty shelves at supermarkets, and electricity rationing, Venezuela has a serious shortage of medicines, including life-saving anti-HIV drugs. This led a network of Venezuelans living with HIV to seek “urgent humanitarian aid” in June 2016 from the Geneva, Switzerland–based Global Fund to Fight AIDS, Tuberculosis and Malaria. [ScienceInsider] Editorial
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EVENTSNEW Standardization of the Hematopoietic Progenitor Assay Training Course NEW Applications of the Hematopoietic Progenitor Assay Training Course Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation) Scientist – Regulatory Support (Cook MyoSite, Inc.) Research Group Leader – Leukemia Research (Department of Biomedicine, University Hospital Basel) Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame) 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 8.05 | Feb 7 2017