Hematopoiesis News 8.02 January 17, 2017 | |
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TOP STORYPrecision Oncology for Acute Myeloid Leukemia Using a Knowledge Bank Approach Considerable between-patient heterogeneity in driver mutations complicates evidence-based personalization of cancer care. By reanalyzing data from 1,540 patients with acute myeloid leukemia, scientists explored how large knowledge banks of matched genomic-clinical data can support clinical decision-making. [Nat Genet] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors generated induced pluripotent stem cells (iPSCs) from acute myeloid leukemia (AML) patient samples harboring MLL rearrangements and found that they retained leukemic mutations but reset leukemic DNA methylation/gene expression patterns. AML-iPSCs lacked leukemic potential, but when differentiated into hematopoietic cells, they reacquired the ability to give rise to leukemia in vivo and reestablished leukemic DNA methylation/gene expression patterns, including an aberrant MLL signature. [Cell Stem Cell] Abstract | Graphical Abstract B cell adaptor for PI3-kinase (BCAP) is a signaling adaptor expressed in mature hematopoietic cells including monocytes and neutrophils. Researchers investigated the role of BCAP in the homeostasis and development of these myeloid lineages. [Blood] Abstract Investigators showed that activation-induced cytidine deaminase (Aid) loss in mice leads to expansion of myeloid cells and reduced erythroid progenitors resulting in anemia, with dysregulated expression of Cebpa and Gata1, myeloid/erythroid lineage specific transcription factors. Consistent with data in the murine context, silencing of AID in human bone marrow cells skews differentiation towards myelomonocytic lineage. [Blood] Abstract A1 is a pro-survival BCL-2-like protein that is expressed predominantly in hematopoietic cells, and the authors describe the characterization of a novel mouse strain that lacks all three functional isoforms of A1 (A1-a, A1-b and A1-d). Complete loss of A1 caused only minor defects, with significant, although relatively small, decreases in γδTCR T cells, antigen-experienced conventional as well as regulatory CD4 T cells and conventional dendritic cells. [Cell Death Differ] Abstract Researchers hypothesized that coordination of hematopoietic stem cell (HSC) specification with vessel patterning might involve modulatory regulatory factors such as R-spondin (Rspo1), an extracellular protein that enhances β-catenin-dependent Wnt signaling and has previously been shown to regulate intersegmental vessel patterning. They found that Rspo1 is required for HSC specification through control of parallel signaling pathways controlling HSC specification: Wnt16/DeltaC/DeltaD and Vegfa/Tgfβ1. [Development] Abstract miRNA182 Regulates Percentage of Myeloid and Erythroid Cells in Chronic Myeloid Leukemia The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia. To find a potential molecular regulator contributing to lineage distribution and TKI resistance, scientists undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). [Cell Death Dis] Full Article Investigators characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with myelodysplasia-related changes, a well-recognized clinical subtype of secondary AML, and de novo AML. They observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. [Sci Rep] Full Article Thrombocytopenia is frequently encountered in infants with necrotizing enterocolitis (NEC). To develop a preclinical model of NEC-related thrombocytopenia, the authors measured serial platelet counts in 10-day-old mouse pups with trinitrobenzene sulfonic acid-induced NEC-like injury. They also measured platelet volume indices, immature platelet fraction, and megakaryocyte number/ploidy in these animals. [Pediatr Res] Abstract CLINICAL RESEARCHHaploidentical Transplantation with Post-Infusion Cyclophosphamide in Advanced Hodgkin Lymphoma Researchers investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. [Leukemia] Abstract Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The scientists assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a Phase I/IIa trial. [Leukemia] Abstract | |
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REVIEWSWhile hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many myeloid malignancies, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification. Immune checkpoint inhibition, in particular along the programmed cell death protein 1/B7-H1 axis, is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies. [Ann Hematol] Abstract Polycomb Complexes PRC1 and Their Function in Hematopoiesis The authors focus on polycomb repressive complex 1 (PRC1) complexes, reviewing recent evidence on their intricate architecture, the diverse mechanisms of their recruitment to targets and on the different ways in which they engage in transcriptional control. They also discuss hematopoietic PRC1 gain-of- and loss-of-function mouse strains, including those that model leukemic and lymphoma diseases, in the belief that these genetic analysis provide the ultimate test bench for molecular mechanisms driving normal hematopoiesis and hematological malignancies. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSThe University of Pittsburgh and Bayer have established a master collaboration agreement to advance research for heart, lung, and blood disease indications. This broad collaboration spans from early research studies to drug development and big data analysis including real-world evidence studies. In addition to the research partnership, Bayer will be supporting an independent investigator-initiated clinical trial in sickle cell disease. [University of Pittsburgh] Press Release ViraCyte Granted U.S. FDA Fast Track Designation for Viralym-C ViraCyte, LLC announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Viralym-C, ViraCyte’s T cell immunotherapy product designed to treat refractory cytomegalovirus infections in patients following a stem cell transplant. [ViraCyte, LLC (PR Newswire Association LLC.)] Press Release | |
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POLICY NEWSCroatia’s Science Minister Rejects Calls to Resign amid Plagiarism Scandal In a plagiarism scandal in Croatia, the country’s highest-level research ethics committee is clashing with its science minister — who says he won’t step down after the committee found he had copied another scholar’s work. Scientists say the case raises questions about academic integrity at the top of a research system that is already riven with misconduct allegations. [Nature News] Editorial
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EVENTSNEW Interventional Orthopedics Foundation 2017 Annual Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Scientist – Regulatory Support (Cook MyoSite, Inc.) NEW Scientist – Regulatory Affairs (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) Postdoctoral Fellowship – Pharmaceutics/Cancer Biology (Ohio State University) 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 8.02 | Jan 17 2017