Hematopoiesis News 8.14 April 11, 2017 | |
| |
TOP STORYProgenitor T-Cell Differentiation from Hematopoietic Stem Cells Using Delta-Like-4 and VCAM-1 The authors describe a fully defined engineered in vitro niche capable of guiding T-lineage development from hematopoietic stem and progenitor cells (HSPCs). The engineered thymus-like niche enabled in vitro production of mouse Sca-1+cKit+ and human CD34+ HSPC-derived CD7+ progenitor T-cells capable of in vivo thymus colonization and maturation into cytokine-producing CD3+ T-cells. [Nat Methods] Abstract | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Scientists investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. In the context of Hoxa9 overexpression, Syk signaling induced Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. [Cancer Cell] Full Article | Graphical Abstract Pdgf Signaling Guides Neural Crest Contribution to the Hematopoietic Stem Cell Specification Niche Researchers demonstrated in zebrafish that trunk neural crest (NC) physically associate with hematopoietic stem cell (HSC) precursors in the dorsal aorta (DA) just prior to initiation of the definitive hematopoietic program. Preventing association of the NC with the DA lead to loss of HSCs. Their results defined NC as key cellular components of the HSC specification niche that can be profiled to identify unknown HSC specification signals. [Nat Cell Biol] Abstract | Press Release To assess the in vivo leukemogenic activity of constitutively active ABL and ARG, the authors generated a bone marrow transplantation model using the chimeric forms TEL/ABL and TEL/ARG, which have comparable kinase activities. TEL/ABL rapidly induced fatal myeloid leukemia in recipient mice, whereas recipients of TEL/ARG-transduced cells did not develop myeloid leukemia; instead, they succumbed to a long-latency infiltrative mastocytosis that could be adoptively transferred to secondary recipients. [Leukemia] Abstract Single-Cell Analysis Identifies Distinct Stages of Human Endothelial-to-Hematopoietic Transition During development, hematopoietic cells originate from endothelium in a process known as endothelial-to-hematopoietic transition (EHT). To study human EHT, investigators coupled flow cytometry and single-cell transcriptional analyses of human pluripotent stem cell-derived CD34+ cells. The resulting transcriptional hierarchy showed a continuum of endothelial and hematopoietic signatures. [Cell Rep] Full Article | Press Release | Graphical Abstract Researchers assessed efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without locus control region of β-globin gene for treatment of ribosomal protein S19-deficient Diamond-Blackfan anemia. The findings demonstrated that these vectors rescue the proliferation defect and improve erythroid development of transduced RPS19 deficient bone marrow cells. [Mol Ther] Abstract Scientists showed that suppressor of cytokine signaling (SOCS)2 is involved in natural killer (NK) cell development. SOCS2−/− mice showed a high frequency of NK cells in the bone marrow and spleen. Knockdown of SOCS2 was associated with enhanced differentiation of NK cells in vitro, and the transplantation of hematopoietic stem cells (HSCs) into congenic mice resulted in enhanced differentiation in SOCS2−/− HSCs. [Sci Rep] Full Article The authors hypothesized that EVI1 could bind to sites regulating its own transcription. They showed that there is a functional interaction between EVI1 and its promoter, and that the different EVI1 isoforms regulate the transcription of EVI1 transcripts through distinct promoter regions. [Biochim Biophys Acta] Abstract MS4A4A: A Novel Cell Surface Marker for M2 Macrophages and Plasma Cells To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets scientists generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood they found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes. [Immunol Cell Biol] Abstract CLINICAL RESEARCHAlloreactivity: The Janus-Face of Hematopoietic Stem Cell Transplantation Investigators analyzed retrospectively a predefined cohort of 32 838 patients and compared it to 59 692 patients with autologous hematopoietic stem cell transplantation as reference group. They found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival. [Leukemia] Full Article Researchers performed echocardiographic screening on 227 consecutive patients prior to hematopoietic stem cell transplantation, and after transplant. They measured cardiac biomarkers cardiac troponin-I, and soluble suppressor of tumorigenicity 2 prior to transplant, during conditioning, and days later in 26 patients. [Bone Marrow Transplant] Abstract | |
| |
REVIEWSHematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications Based on current preclinical and clinical evidences, among other treatment modalities, hematopoietic stem cell gene therapy could potentially result in robust therapeutic benefit for LSD patients, with particular indication for those characterized by severe brain damage. [Mol Ther] Abstract DNA Damage-Induced Phosphatase Wip1 in Regulation of Hematopoiesis, Immune System and Inflammation The authors summarize the current knowledge on the role of Wip1 in the differentiation of various hematopoietic lineages and how Wip1 deficiency affects the functions of immune cells. [Cell Death Discov] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
SCIENCE NEWSSyros Pharmaceuticals announced that new preclinical data on SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase II clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), were presented. [Press release from Syros Pharmaceuticals discussing research presented at the 2017 American Association for Cancer Research, Washington, D.C.] Press Release | |
| |
INDUSTRY NEWSClinician-Researcher to Lead New Bone Marrow Transplantation Initiative Hematologist-oncologist Ahmad Samer Al-Homsi MD, MBA, will lead a new bone marrow transplantation program at NYU Langone’s Perlmutter Cancer Center for treating blood-borne cancers, including leukemia, lymphoma and multiple myeloma, and potentially utilize transplantation as an adjunct to immunotherapy for solid tumors. He also will investigate ways to reduce graft-versus-host disease, in which immune cells in donated blood and marrow attack the tissues of a recipient. [NYU Langone (PR Newswire Association LLC.)] Press Release Kite Pharma, Inc. announced that it won the Clinical Trial Result of the Year award for ZUMA-1, its pivotal CAR-T trial of axicabtagene ciloleucel, in patients with refractory aggressive B-cell non-Hodgkin lymphoma at the Clinical and Research Excellence Awards. The award recognizes clinical achievements in the pharmaceutical industry and contribution to the advancement of therapies for unmet medical needs. [Kite Pharma, Inc.] Press Release ASH Awards $750k to Preserve Promising Biomedical Research The American Society of Hematology (ASH) announced the names of five investigators whose research has been awarded $150,000 as part of the eighth round of ASH Bridge Grants. Designed to sustain promising hematologic research proposals that score well but cannot be funded by NIH due to stagnant and uncertain funding, the ASH Bridge grants will preserve programs at five institutions across the United States. [The American Society of Hematology (PR Newswire Association LLC.)] Press Release ERYTECH Announces Launch of Investigator-Initiated Phase II Study of Eryaspase (GRASPA®) for ALL ERYTECH Pharma announced the launch of an investigator-initiated study to evaluate eryaspase, also known by the trade name GRASPA®, in patients with acute lymphoblastic leukemia (ALL). The study will take place in seven Nordic countries and be conducted in collaboration with the Nordic Society of Pediatric Hematology and Oncology. [ERYTECH Pharma] Press Release Alexo Therapeutics announced that it has initiated dosing in its Phase I clinical program evaluating the safety of ALX148 in patients with advanced solid tumors and lymphoma. [Alexo Therapeutics] Press Release | |
| |
POLICY NEWSReview of Canadian Science Calls for Better Oversight, Coordination — and More Money To reinvigorate its science base, Canada needs to “reinvest” almost CAD$500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial U.S. Report Calls for Research Integrity Board The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial Critics Worry Faster FDA Drug Reviews Could Compromise Safety For biotechs, waiting for new drugs to be approved is not as hard as it used to be. Since late last year, federal regulators have acted months earlier than expected to OK a bumper crop of new drugs from Massachusetts companies. The speedy decisions are welcomed by businesses that have made massive investments in developing experimental medicines and are eager for them to start generating revenue. But critics say the Food and Drug Administration (FDA)’s hurry-up mode may sacrifice patient safety — accelerating under pressure not only from the industry and investors, but from a regulation-averse Trump administration. [Boston Globe Media Partners, LLC] Editorial
| |
EVENTSNEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Postdoctoral Position – Leukemia Research (VIB-KU Leuven Center for Cancer Biology) Scientist – Biological Function of Hematopoietic Stem Cells/Progenitors (HemoGenyx LLC) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University) Principal Scientist – Immuno Oncology (Celgene Corporation) Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation) Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation) Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute) Principal Scientist – Translational Development (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) 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.
| |
Have we missed an important article or publication in Hematopoiesis News? Click here to submit! Comments or suggestions? Submit your feedback here. | |
|