Hematopoiesis News 7.47 November 29, 2016 | |
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TOP STORYNUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis The nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in multiple hematopoietic malignancies. Investigators demonstrated that NUP98 fusion proteins, including NUP98-HOXA9, NUP98-HOXD13, NUP98-NSD1, NUP98-PHF23, and NUP98-TOP1 physically interact with mixed lineage leukemia 1 (MLL1) and the non-specific lethal (NSL) histone-modifying complexes. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Investigators demonstrated how individual hematopoietic stem/progenitor cell engraft in long bones by thinning one side of the tibia for direct and unbiased observation. Intravital imaging enabled detailed visualization of single Sca-1+, c-Kit+, Lineage– cell migration to bone marrow niches and subsequent proliferation to reconstitute hematopoiesis. [Leukemia] Abstract Antibiotics Impair Murine Hematopoiesis by Depleting Intestinal Microbiota Recent advances in the understanding of steady-state hematopoiesis have allowed scientists to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. [Blood] Abstract Researchers investigated the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. They showed that there are dynamic changes in Ryk expression during development and in different hematopoietic tissues. Functionally, Ryk regulates NK cell development in a temporal fashion. [Cell Death Dis] Full Article GRK6 Regulates ROS Response and Maintains Hematopoietic Stem Cell Self-Renewal The authors demonstrated that G protein-coupled receptor kinase (GRK) 6 knockout (GRK6−/−) mice exhibit lymphocytopenia, loss of the hematopoietic stem cell (HSC) and multiple progenitor populations. GRK6 deficiency leads to compromised lymphoid differentiation, largely owing to the impairment of HSC self-renewal. [Cell Death Dis] Full Article Scientists report an unknown function of CXCR4/CXCL12 axis in the protection of hematopoietic stem cells (HSCs) against oxidative stress. Disruption of CXCR4 receptor in mice leads to increased endogenous production of reactive oxygen species, resulting in p38 MAPK activation, increased DNA double-strand breaks and apoptosis leading to marked reduction in HSC repopulating potential. [Sci Rep] Full Article The authors demonstrated that constitutive expression of Vent-like homeobox gene (VENTX) suppresses expression of genes responsible for terminal erythroid differentiation in normal CD34+ stem and progenitor cells. Transplantation of bone marrow progenitor cells retrovirally engineered to express VENTX caused massive expansion of primitive erythroid cells and partly acute erythroleukemia in transplanted mice. [Oncotarget] Full Article Researchers studied the phenotype of peritoneal leukemia-associated macrophages (Per LAMs), their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model. Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and Arg1, which was not commonly observed in macrophages from different origins. [Mol Immunol] Abstract CLINICAL RESEARCHEGR2 Mutations Define a New Clinically Aggressive Subgroup of Chronic Lymphocytic Leukemia Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening and two validation cohorts. Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. [Leukemia] Abstract PD-1 Checkpoint Blockade in Patients with Relapsed AML after Allogeneic Stem Cell Transplantation Monoclonal antibodies directed against inhibitory immune checkpoint receptors CTLA-4 and PD-1 have shown substantial therapeutic activity in solid cancers, but also in selected hematological neoplasias such as Hodgkin’s lymphoma. Unlike conventional therapeutic approaches, which employ agents that directly act on cancer cells, checkpoint blockade harnesses the immune system’s inherent ability to eradicate cancer by fine-tuning physiological processes, that is, unleashing suppressed immune responses. [Bone Marrow Transplant] Abstract | |
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REVIEWSA View of Human Hematopoietic Development from the Petri Dish Human pluripotent stem cells provide an unparalleled opportunity to establish in vitro differentiation models that will transform our approach to the study of human development. In the case of the blood system, these models will enable investigation of the earliest stages of human embryonic hematopoiesis that was previously not possible. In addition, they will provide platforms for studying the origins of human blood cell diseases and for generating de novo hematopoietic stem and progenitor cell populations for cell-based regenerative therapies. [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 NEWSSkylineDx announced the presentation of new data that demonstrate the prognostic value of MMprofilerâ„¢ SKY92 gene signature, a gene expression profiling test for multiple myeloma (MM), as part of an integrated approach to identifying patients at ultra-high risk of MM. The data will be presented in a poster session. [Press release from SkylineDx (PR Newswire Association LLC.) discussing research to be presented at the 58th American Society of Hematology (ASH), San Diego] Press Release PharmaEssentia Announces Phase III PROUD-PV Study Results to be Presented PharmaEssentia Corporation announced that the company’s lead therapeutic candidate, ropeginterferon alfa-2b, will be featured in an oral presentation of the Phase III PROUD-PV study results for first-line treatment of polycythemia vera (PV), a type of blood cancer marked by elevated red blood cell production.. [Press release from PharmaEssentia Corporation (PR Newswire Association LLC.) discussing research to be presented at the 58th American Society of Hematology (ASH), San Diego] Press Release | |
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INDUSTRY NEWSEMD Serono Inc. announced that the US Food and Drug Administration (FDA) has accepted for Priority Review EMD Serono’s Biologics License Application for avelumab. This review relates to avelumab’s proposed use in patients with metastatic Merkel cell carcinoma, based on tumor response results from the JAVELIN Merkel 200 trial. [EMD Serono Inc.] Press Release The Global Good Fund, The Feinstein Institute for Medical Research at Northwell Health and Sanguistat, Inc., are partnering on clinical trials of the Neural TourniquetTM to evaluate the efficacy of bioelectronic medicine in treating blood loss associated with postpartum hemorrhage. [Sanguistat, Inc.] Press Release | |
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POLICY NEWSCongress Poised to Pass Sweeping Biomedical Innovation Bill Congress is poised to approve a massive piece of legislation that would provide the National Institutes of Health with $4.8 billion over the next decade for a set of research initiatives, including brain and cancer research and efforts to develop so-called precision medicine treatments that are tailored to an individual’s genetic makeup. [ScienceInsider] Editorial Spanish Military Flies Lab Animals to Canary Islands after Airlines Refuse to Take Them on Board Twenty-nine transgenic mice that two Spanish airlines had refused to transport hitched a ride to the Canary Islands on a military plane Friday and are now at their final destination, the University of La Laguna on Tenerife in Spain. The mice, bred in the United States, had been stranded in Madrid for two months because Iberia and Air Europa have stopped shipping laboratory animals. [ScienceInsider] Editorial
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EVENTSNEW 2017 European Cancer Congress Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Principal Scientist – Translational Development (Celgene Corporation) NEW Associate Director – Translational Development (Celgene Corporation) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC) Postdoctoral Fellowship – Stem Cell and Red Cell Biology (Lund University) Postdoctoral Fellow(s) – Various Projects (Cincinnati Children’s Hospital Medical Center) Postdoctoral Fellow – Stem Cell Biology and Hematology (Center for Cell-Based Therapy) Postdoctoral Fellow – Proteomic Hematology (Lund University) Research Associate – Hematology (Editas Medicine) Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation) Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes) 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 7.47 | Nov 29 2016