Hematopoiesis News 8.23 June 13, 2017 | |
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TOP STORYResearchers provide evidence for mutations in MAP kinase signaling intermediates in CD34+ cells from patients with Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH)/ECD, including detection of shared origin of LCH and acute myelomonocytic leukemia driven by TET2-mutant CD34+ cell progenitors in one patient. They demonstrated functional self-renewal capacity for CD34+ cells to drive the development of histiocytosis in xenotransplantation assays in vivo. [Blood] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)To investigate the requirement and timing of all bone morphogenetic protein (BMP) signaling in hematopoietic stem cell ontogeny, the authors used a transgenic line, which inducibly expresses an inhibitor of BMP signaling, Noggin, as well as a chemical inhibitor of BMP receptors, DMH1, and described the inputs from BMP signaling into the definitive hemangioblast gene regulatory network and the hemogenic endothelium, as well as into primitive hematopoiesis. [Proc Natl Acad Sci USA] Full Article RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML Researchers compared the transcriptional networks of two types of acute myeloid leukemia (AML) with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins displayed distinct binding patterns, showed differences in gene expression and chromatin landscape, and were dependent on different transcription factors. [Cell Rep] Full Article | Press Release | Graphical Abstract The authors developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34+-hematopoietic stem and progenitor cells (HSPCs) and induced the t(11;19)/MLL-ENL translocation. Leveraging this system they demonstrated that HSPCs harboring the translocation showed only a transient clonal growth advantage in vitro. [Haematologica] Abstract | Full Article Bone Marrow Adipocytes Support Hematopoietic Stem Cell Survival The role of bone marrow-adipocytes (BM-As) was explored by studying primary human BM-As isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human hematopoietic stem cells by the long-term culture initiating cell assay. [J Cell Physiol] Abstract Genetic Background Influences Susceptibility to Chemotherapy-Induced Hematotoxicity Scientists sought to identify genomic loci that influence chemotherapy-induced hematotoxicity by dosing diversity outbred mice with one of three chemotherapy drugs; doxorubicin, cyclophosphamide or docetaxel. They observed that each drug had a distinct effect on both the changes in blood cell subpopulations and the underlying genetic architecture of hematotoxicity. [Pharmacogenomics J] Abstract Researchers characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. [BMC Immunol] Full Article CLINICAL RESEARCHHematopoietic Stem Cell Transplantation in Patients with Gain of Function STAT1 Mutation Investigators sought to aggregate the worldwide experience of hematopoietic stem cell transplantation in gain of function mutations in signal transducer and activator of transcription 1 (GOF-STAT1) patients and to assess outcomes including donor engraftment, overall survival, graft versus host disease, and transplant related complications. Primary donor engraftment in this cohort of 15 GOF-STAT1 patients was 74% and overall survival was only 40%. [J Allergy Clin Immunol] Abstract Scientists sought to investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory primary CNS lymphoma (PCNSL). 22 patients responded to induction and 32 patients commenced HCT-ASCT. 22 patients achieved complete remission after HCT-ASCT. [Leukemia] Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. Investigators developed a novel method of graft manipulation based on negative depletion of αβ T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. [Blood] Abstract SEMA3A Partially Reverses VEGF Effects through Binding to Neuropilin-1 Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, the authors found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34+ hematopoietic stem cells and semaphorin 3A (SEMA3A) in bone marrow stromal cells (BMSCs). They found higher VEGFA expression in de novo acute myeloid leukemia patients group and higher SEMA3A expression in all BMSCs patient’s samples compared to control group. [Stem Cell Res] Full Article | |
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REVIEWSAdult Hematopoietic Stem Cell Niches Scientists discuss how recent advances have improved the understanding of the niches that maintain adult hematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. [Nat Rev Immunol] Abstract Genetic Predisposition to Hematologic Malignancies: Management and Surveillance The authors summarize and integrate expert consensus recommendations and medical management considerations for the patient newly diagnosed with a leukemia predisposition disorder. Indications to consider additional studies and referral for allogeneic stem cell transplantation are also discussed. [Blood] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSArog Pharmaceuticals Announces Clinical Presentations on Crenolanib Arog Pharmaceuticals, Inc. announced that it will feature two poster presentations and a satellite symposium on the company’s lead product candidate, crenolanib. Crenolanib continues to demonstrate best-in-class properties in the treatment of acute myeloid leukemia with FLT3 mutations. [Press release from Arog Pharmaceuticals, Inc. (GlobeNewswire, Inc.) discussing research to be presented at the 2017 Congress of the European Hematology Association (EHA), Madrid] Press Release Novartis announced findings from an interim analysis of its multi-center Phase II JULIET study of CTL019 in adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL). [Press release from Novartis AG discussing research presented at the 2017 International Conference on Malignant Lymphoma (ICML) Meeting, Lugano] Press Release | |
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INDUSTRY NEWSDragonfly Therapeutics, Inc. announced a global strategic collaboration with Celgene Corporation and its affiliates to discover, develop and commercialize innovative immuno-oncology treatment options for patients with hematological malignancies based on Dragonfly’s NK cell based TriNKET™ technology platform. [Dragonfly Therapeutics, Inc. (PR Newswire Association LLC.)] Press Release Merck provided an update on two combination studies of KEYTRUDA®, the company’s anti-PD-1 therapy, in the blood cancer multiple myeloma. Merck has accepted the external Data Monitoring Committee recommendation to pause new enrollment on KEYNOTE-183 and KEYNOTE-185, two studies exploring KEYTRUDA treatment in combination with other therapies in multiple myeloma. The pause is to allow for additional information to be collected to better understand more reports of death in the KEYTRUDA groups. [Merck & Co., Inc.] Press Release Prof Receives Funding to Study Avocado Compound as Potential Cancer Treatment New funding will allow a University of Guelph professor to study use of avocado compounds in fighting cancer. Food science professor Paul Spagnuolo will begin a four-year, $200,000 study of an avocado-derived leukemia drug. [University of Guelph] Press Release | |
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POLICY NEWSCan Fake Names Tease Out NIH Reviewer Bias? When the label “white male” is attached to a research grant application, do peer reviewers give it a better score? That’s the question psychologist Patricia Devine of the University of Wisconsin in Madison has spent the past four years, and more than $1 million from the National Institutes of Health (NIH) in Bethesda, Maryland, trying to answer with an unusual experiment. [ScienceInsider] Editorial Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial Trump Names Sharpless to Lead U.S. Cancer Institute President Donald Trump announced his intention to appoint Norman “Ned” Sharpless to be the next director of the National Cancer Institute in Bethesda, Maryland. Sharpless, who is 50 years old, is a physician and currently director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. He also holds an academic appointment at the university’s school of medicine. [ScienceInsider] Editorial
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EVENTSNEW Keystone Symposia: Regenerative Biology and Applications: Cell Differentiation, Tissue Organization and Biomedical Engineering Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals) Postdoctoral Fellow – Stem Cell Biology and Epigenetics (University of South Carolina) Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering) Faculty Position – Normal and Malignant Hematopoiesis (Cincinnati Children’s Hospital) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) Principal Scientist – Immuno Oncology (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) 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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