Hematopoiesis News 9.22 June 5, 2018 | |
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TOP STORYPenn-Developed Approach Could Limit Toxicity of CAR T Cell Therapy in Acute Myeloid Leukemia A new approach may provide a new path towards treating acute myeloid leukemia with CAR T cells. [Press release from the University of Pennsylvania discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors showed that splice alteration of HNRNPA2B1, a splicing factor differentially bound and spliced by SRSF2P95H, impairs hematopoietic differentiation in vivo. [Leukemia] Abstract Functional Compensation between Hematopoietic Stem Cell Clones In Vivo Researchers showed how individual HSC clones heterogeneously compensate for the lymphopoietic deficiencies of other HSCs in a mouse. This compensation rescues the overall blood supply and influences blood cell types outside of the deficient lineages in distinct patterns. They found that highly differentiating HSC clones expand their cell numbers at specific differentiation stages to compensate for the deficiencies of other HSCs. [EMBO Rep] Abstract | Press Release 1 | Press Release 2 | Graphical Abstract Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine granulocytic-monocytic (GM)-lineage differentiation, scientists unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. [Cell Rep] Full Article | Graphical Abstract In order to investigate phenotype and the expression of homing molecules, CD34, CD133, CD90, CD45RA, CD26 and CD9 expression was determined on sorted CD34+ cells according to CXCR4 and CD133 expression before and after ex vivo expansion. [Haematologica] Abstract | Full Article Scientists innovated a unique system, which involved generating GATA2 knockout human embryonic stem cell lines with conditional GATA2 expression. They demonstrated that GATA2 activity is not required for VE-cadherin+CD43–CD73+ non-hemogenic endothelium (HE) or VE-cadherin+CD43–CD73– HE generation and subsequent HE diversification into DLL4+ arterial and DLL4– non-arterial lineages. [Stem Cell Reports] Full Article | Graphical Abstract Researchers found that the expression of Pin1 mRNA and protein was significantly increased in both de novo leukemia clinical samples and multiple leukemia cell lines, compared with healthy controls. Genetic or chemical inhibition of Pin1 in human multiple leukemia cell lines potently inhibited multiple Pin1 substrate oncoproteins and effectively suppressed leukemia cell proliferation and colony formation ability in cell culture models in vitro. [J Hematol Oncol] Full Article By implementing an adherent culture, serum-free differentiation system, which utilizes a small molecule CHIR99021 to induce hPSCs toward various hematopoietic lineages, researchers established that, compared to OP9 co-culture hematopoietic induction system, the application of CHIR99021 alters the early steps of hematopoiesis such as hemangioblast, angiogenic hematopoietic progenitors and hemogenic endothelium. [Exp Hematol] Abstract | Graphical Abstract CLINICAL RESEARCHQuizartinib is an oral, highly potent, and selective next-generation FLT3 inhibitor with clinical antileukemic activity in relapsed or refractory acute myeloid leukemia. The authors aimed to assess the efficacy and safety of single-agent quizartinib in patients with relapsed or refractory acute myeloid leukemia. [Lancet Oncol] Abstract Investigators conducted a Phase I study involving 26 patients with progressive, relapsed, or refractory chronic lymphocytic leukemia (CLL). Inhibition of ROR1 signaling was observed, including decreased activation of RhoA and HS1. Transcriptome analyses showed that therapy inhibited CLL stemness gene expression signatures in vivo. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract Scientists combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab, followed by lenalidomide/rituximab maintenance. [Ann Hematol] Full Article | |
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REVIEWSMyeloid Cell Contributions to Cardiovascular Health and Disease Inflammatory cells, such as monocyte-derived macrophages, and their actions and products are increasingly being considered as potential drug targets for treatment of atherosclerosis, myocardial infarction and heart failure. Particularly promising developments are the identification of harmful arterial and cardiac macrophage subsets, the cells’ altered, sometimes even clonal production in hematopoietic organs, and epigenetically entrained memories of myeloid progenitors and macrophages in the setting of cardiovascular disease. [Nat Med] Abstract Oncogenic Roles of EZH1/2 in Hematological Malignancies The histone methyltransferases enhancer of zeste homolog 1 and 2 (EZH1/2), which are subunits of polycomb repressive complexes (PRCs), are recurrently mutated or highly expressed in many hematological malignancies. EZH2 has a dual function in tumorigenesis as an oncogene and tumor suppressor gene, and targeting PRC2, in particular EZH1/2, for anticancer therapy has been extensively developed in the clinical setting. [Cancer Sci] Abstract Improvements in conditioning, infectious disease monitoring and management, histocompatibility testing and graft selection have successively improved outcomes, primarily due to a reduction in non-relapse mortality. Unfortunately, disease relapse remains a significant cause of treatment failure in both acute myeloid leukemia and acute myeloid leukemia. [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 NEWSSeattle Genetics, Inc. highlighted data from the Phase III ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in newly diagnosed stage III or IV classical Hodgkin lymphoma. [Press release from Seattle Genetics, Inc. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from a pre-planned interim analysis of the Phase III iNNOVATE study evaluating Imbruvica® in combination with rituximab in relapsed/refractory and treatment-naïve patients with Waldenström’s macroglobulinemia. [Press release from Janssen Global Services, LLC discussing research presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release | |
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INDUSTRY NEWSAmgen and The University of Texas MD Anderson Cancer Center announced two multi-year collaboration agreements aimed at accelerating development of a variety of Amgen’s early-stage oncology therapies for patients with leukemia, myelodysplastic syndromes, multiple myeloma, small-cell lung cancer, and other non-lung cancers with small-cell histologies. [Amgen Inc.] Press Release GlycoMimetics, Inc. announced it had signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). Under the terms of the CRADA, GlycoMimetics will collaborate with both the NCI and the Alliance for Clinical Trials in Oncology to conduct a randomized, controlled clinical trial testing the addition of GMI-1271 to a standard cytarabine/daunorubicin regimen in older adults with previously untreated acute myelogenous leukemia (AML) who are suitable for intensive chemotherapy. [GlycoMimetics, Inc.] Press Release Adaptive Biotechnologies announced that it entered into an agreement with Sanofi to utilize Adaptive’s NGS-based clonoSEQ® Assay to assess minimal residual disease status in response to isatuximab. This investigational anti-CD38 monoclonal antibody is in clinical development for the treatment of newly diagnosed, relapsed and/or refractory multiple myeloma. [Adaptive Biotechnologies] Press Release FDA Expedites Review of Novartis Drug Promacta® for First-Line Severe Aplastic Anemia (SAA) Novartis announced that the FDA has accepted the company’s supplemental New Drug Application and granted Priority Review designation to Promacta® in combination with standard immunosuppressive therapy for first-line treatment of SAA. [Novartis AG] Press Release Astellas Pharma Inc. announced that the FDA has accepted, with Priority Review, the company’s New Drug Application for gilteritinib for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia with a FLT3 mutation as detected by an FDA-approved test. [Astellas Pharma Inc.] Press Release Bristol-Myers Squibb Company announced that the FDA lifted a partial clinical hold placed on CA209-602, a randomized, open-label Phase III study evaluating the addition of Opdivo to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. [Bristol-Myers Squibb Company] Press Release | |
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POLICY NEWSEurope’s Top Science Funder Shows High-Risk Research Pays Off A popular and unusual self-review carried out by Europe’s most prestigious science funder is back. The annual assessment, now in its third year, found that nearly one in five projects by the European Research Council led to a scientific breakthrough. [Nature News] Editorial ‘Right-to-Try’ Law Intended to Weaken the FDA, Measure’s Sponsor Says in Blunt Remarks Sen. Ron Johnson, the author of the federal “right-to-try” law signed by President Trump, wants to make one thing clear: His new law is meant to weaken the FDA. “This law intends to diminish the FDA’s power over people’s lives, not increase it,” he wrote in a letter to Commissioner Scott Gottlieb. [STAT News] Editorial China to Crack Down on Fraud in Scandal-Hit Scientific Research amid ZTE Wrangle China has issued the first national guidelines to enforce academic integrity in scientific research and vowed to punish academics and institutes for misconduct such as plagiarism and fabrication of data. [South China Morning Post Publishers Ltd] Editorial Sweden Commits to Open Science with New Open-Access Publishing Deal Swedish researchers can now publish their articles in Frontiers’ Open Access journals through a simplified process that covers publishing fees, thanks to a national agreement announced between Frontiers and the National Library of Sweden, on behalf of the organizations participating in the Bibsam Consortium. [American Association for the Advancement of Science] Editorial
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EVENTSNEW LabRoots: 6th Annual Cancer Research & Oncology Virtual Event Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW PhD Student – Tumor Immunology (University Medical Center Utrecht) Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine) Cancer Researchers – Hematologic Malignancy (Cedars-Sinai Medical Center) Postdoctoral Fellow – Hematopoiesis and Leukemia (University of Pennsylvania) Group Leader – Leukemia Research (Hospital del Mar Research Institute) Postdoctoral Fellow – B-Cell Lymphoma (University of Texas Health Science Center at San Antonio) Postdoctoral Position – Stem Cell and Cancer Research (Institute for Research in Biomedicine) Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory) Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine) Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia) 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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