Hematopoiesis News 10.05 February 12, 2019 | |
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TOP STORYInvestigators showed that an anti-human CD117 mAb, SR-1, inhibited normal cord blood and bone marrow HSCs in vitro. Anti-CD117 mAbs also facilitated the engraftment of normal donor human HSCs in myelodysplastic syndrome (MDS) xenograft mouse models, restoring normal human hematopoiesis and eradicating aggressive pathologic MDS cells. [Blood] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)In a novel myelofibrosis model established by transplantation of vitamin D receptor (VDR)+/+ hematopoietic stem/progenitor cells into VDR-/- mice, donor-derived F4/80+ macrophages proliferated together with recipient-derived α-smooth muscle actin+ myofibroblasts, both of which comprised fibrotic tissues with an indistinguishable spindle-shaped morphology. [Blood] Abstract | Press Release Researchers studied wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts grouped into twelve clusters. They revealed that some clusters likely represented consecutive differentiation states toward a contractile phenotype, while others appeared to represent distinct fibroblast lineages. One subset of fibroblasts expressed hematopoietic markers, suggesting their myeloid origin. [Nat Commun] Full Article | Press Release By using an embryonic stem cell-derived myeloid progenitor cell model, scientists found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. [Autophagy] Abstract EDA Fibronectin-TLR4 Axis Sustains Megakaryocyte Expansion and Inflammation in Bone Marrow Fibrosis Fibronectin EDA isoform bound to TLR4 and sustained progenitor cell proliferation and megakaryopoiesis in a thrombopoietin (TPO)-independent fashion, inducing LPS-like responses, such as NF-κB activation and release of profibrotic IL-6. Pharmacological inhibition of TLR4 or TLR4 deletion in TPO mimetic romiplostim mice abrogated Mk hyperplasia, bone marrow fibrosis, IL-6 release, extramedullary hematopoiesis, and splenomegaly. [J Exp Med] Abstract The Developmental Stage of the Hematopoietic Niche Regulates Lineage in MLL-Rearranged Leukemia The authors used heterochronic transplantation of leukemia driven by MLL/KMT2A translocations to investigate the contribution of the age of the hematopoietic microenvironment to age-specific leukemia phenotypes. [J Exp Med] Abstract Scientists demonstrated that c-Myc was required for S100A9-induced upregulation of PD-1/PD-L1, and that treatment of myelodysplastic syndrome hematopoietic stem and progenitor cells with anti-PD-1 antibody suppressed the expression of Myc target genes and increased the expression of hematopoietic pathway genes. [Leukemia] Full Article Both spaceflight and simulated microgravity significantly decreased the number of hematopoietic stem and progenitor cells, mainly by blocking cell cycle at G1/S transition, but did not affect their differentiation abilities. RNA-sequencing data indicated that genes related to cell proliferation were down-regulated, whereas the genes related to cell death were up-regulated under microgravity. [FASEB J] Abstract PTK787/vatalanib, a tyrosine kinase inhibitor selective for vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2, and neutralizing anti-VEGFR2 monoclonal antibody DC101 blocked enhancement of hematopoietic stem and progenitor cell mobilization by FG-4497. VEGFR2 was absent on mesenchymal and hematopoietic cells and was detected only in Sca1+ endothelial cells in the bone marrow. [Blood Adv] Abstract | Graphical Abstract CLINICAL RESEARCHEpigenetic Age Is a Cell-Intrinsic Property in Transplanted Human Hematopoietic Cells Investigators found that the DNA methylation (DNAm) age of reconstituted blood was not influenced by the recipient’s age, even 17 years after HSC transplantation, in individuals without relapse of their hematologic disorder. However, the DNAm age of recipients with relapse of leukemia was unstable. [Aging Cell] Full Article Circulating hematopoietic stem/progenitor cells (HSPCs) frequency was 1.8-fold higher in coronary heart disease (CHD) patients than non-CHD participants. Multivariate-adjusted logistic analysis demonstrated that HSPCs were the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis. [Sci Rep] Full Article Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSHematopoietic Stem Cell Activity and Interactions with the Niche The authors review advances in the understanding of HSC regulation by niches during homeostasis, aging and cancer, and they discuss their implications for the development of therapies to rejuvenate aged HSCs or niches or to disrupt self-reinforcing malignant niches. [Nat Rev Mol Cell Biol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSuniQure N.V. announced updated clinical data in patients treated in the company’s ongoing Phase IIb study of AMT-061, an investigational AAV5-based gene therapy containing a patent-protected FIX-Padua variant, for the treatment of patients with severe and moderately severe hemophilia B. [Press release from uniQure N.V. discussing research presented at the Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), Prague] Press Release | |
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INDUSTRY NEWSCellect Biotechnology Ltd. announced a collaboration with Washington University aimed at determining the safety and tolerability in a US Phase I/II study using ApoGraft™ for bone marrow transplantations. [Cellect Biotechnology Ltd. (PR Newswire Association LLC.)] Press Release AbbVie and Teneobio Announce a Strategic Transaction to Develop a New Treatment for Multiple Myeloma AbbVie, Teneobio, Inc. and its affiliate TeneoOne, Inc. announced that they have entered a global strategic transaction to develop and commercialize TNB-383B, a BCMA-targeting immunotherapeutic for the potential treatment of multiple myeloma. [AbbVie Inc.] Press Release FDA Approves First Therapy for the Treatment of Adult Patients with a Rare Blood Clotting Disorder The FDA approved Cablivi injection, the first therapy specifically indicated, in combination with plasma exchange and immunosuppressive therapy, for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura, a rare and life-threatening disorder that causes blood clotting. [US Food and Drug Administration] Press Release Takeda Pharmaceutical Company Limited announced that the European Commission extended the current marketing authorization of ADCETRIS to include treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD. ADCETRIS is an antibody-drug conjugate directed at CD30, a defining marker of Hodgkin lymphoma. [Takeda Pharmaceutical Company Limited] Press Release Bristol-Myers Squibb Company announced that the European Commission has approved sprycel in combination with chemotherapy for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. [Bristol-Myers Squibb Company] Press Release Moleculin Announces Approval for Third Drug to Commence Clinical Trials Moleculin Biotech, Inc. announced it has received approval to begin clinical trials in Poland for its STAT3 inhibitor, WP1220, for the topical treatment of cutaneous T-cell lymphoma. [Moleculin Biotech, Inc.] Press Release Rafael Pharmaceuticals, Inc. announced that devimistat will be investigated in a new combination for the treatment of T-cell lymphoma under the ‘Tailoring CAR-based immunotherapy strategies to T-Cell Lymphoma’ project as a part of Stand Up To Cancer’s T-cell lymphoma Dream Team Research Grant. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release Karyopharm Therapeutics Inc. announced that the Oncologic Drugs Advisory Committee of the FDA is scheduled to review data supporting the company’s New Drug Application requesting accelerated approval for selinexor, a first-in-class, oral selective inhibitor of nuclear export compound. [Karyopharm Therapeutics Inc.] Press Release | |
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POLICY NEWSFrance Set to Get First National Strategy for Research France is preparing to implement a national, multi-year research plan for the first time – a move warmly welcomed by the heads of the country’s major research agencies. [Nature News] Editorial Trump’s $500 Million for Childhood Cancer? Scientists Have Ideas How to Spend It The pediatric cancer community applauded President Trump’s State of the Union promise of an additional $500 million over the next 10 years to fund research into cures for more childhood cancers. [STAT News] Editorial UC Berkeley Team to Be Awarded CRISPR Patent The University of California (UC), Berkeley, and its partners in developing CRISPR gene editing will receive the patent at the heart of an intellectual property dispute between the Berkeley team and the Broad Institute and its CRISPR collaborators. [The Scientist] Editorial
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EVENTSNEW World Advanced Therapies and Regenerative Medicine Congress 2019 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Research Fellow – Development of Lymphoid Cells (Lund University) Chair – Microbiology and Immunology (Indiana University School of Medicine) Postdoctoral Studies – Normal & Malignant Hematopoiesis (Karolinska Institutet) Investigator Positions – Hematologic Malignancies (University of Alabama Birmingham) Postdoctoral Associate – T-ALL Research (University of New Mexico) Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine) Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine) Assistant Project Scientist – Hematology and Oncology (University of California, Davis) Faculty Positions – Hematology and Oncology (University of California, Davis) 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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