Hematopoiesis News 7.42 October 25, 2016 | |
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TOP STORYThe MCL1 Inhibitor S63845 Is Tolerable and Effective in Diverse Cancer Models The authors describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of myeloid cell leukemia 1 (MCL1). Their mechanistic studies demonstrated that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Depleting Dietary Valine Permits Nonmyeloablative Mouse Hematopoietic Stem Cell Transplantation Researchers report that the essential amino acid valine is indispensable for the proliferation and maintenance of hematopoietic stem cell (HSC). Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. [Science] Abstract | Press Release Deregulation of DUX4 and ERG in Acute Lymphoblastic Leukemia The authors showed that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor acute lymphoblastic leukemia (ALL) that comprises up to 7% of B-ALL. [Nat Genet] Abstract | Press Release MicroRNA-29b Mediates Altered Innate Immune Development in Acute Leukemia Scientists used a mouse model of de novo acute myeloid leukemia (AML) to elucidate the mechanisms by which AML evades natural killer (NK) cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. [J Clin Invest] Full Article Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in bortezomib (BTZ) resistance. Since a low secretory B cell phenotype is associated with BTZ resistance in MM and retinoid signaling promotes plasma cell differentiation and Ig production, scientists investigated whether stromal expression of the cytochrome P450 monooxygenase CYP26 modulates BTZ sensitivity in the BM niche. [J Clin Invest] Full Article Scientists interrogated the replication-independent transcription-coupled-nucleotide excision repair in prospective trial patients, primary chronic lymphocytic leukemia cultures, cell lines, and mice. [Leukemia] Abstract Scientists developed a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34+ blood cell products for transplantation. [Nat Commun] Full Article | Press Release To identify additional therapeutic targets in acute myeloid leukemia (AML), researchers optimized a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and used it to identify genetic vulnerabilities in AML cells. [Cell Rep] Full Article | Graphical Abstract | Press Release Highly Efficient Genome Editing of Murine and Human Hematopoietic Progenitor Cells by CRISPR/Cas9 The authors describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human hematopoietic stem/progenitor cells using the CRISPR/Cas9 system. [Cell Rep] Full Article | Graphical Abstract Comparison of Human Hematopoietic Reconstitution in Different Strains of Immunodeficient Mice Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. [Stem Cells Dev] Abstract CLINICAL RESEARCHThe authors sought to determine rates of RBC-transfusion-independence after therapy with pomalidomide vs. placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion-dependence. [Leukemia] Full Article | |
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REVIEWST Cell Genesis: In Vitro Veritas Est? The authors discuss recent strategies for the generation of T cells from human hematopoietic stem/progenitor cells and pluripotent stem cells in vitro. Continued advancement in the generation of human T cells in vitro will expand their benefits and therapeutic potential in the clinic. [Trends Immunol] Abstract Inhibition of FLT3 in AML: A Focus on Sorafenib The authors summarize the clinical data on sorafenib and other FMS-like tyrosine kinase 3 (FLT3) inhibitors in AML. [Bone Marrow Transplant] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSTLC178 Granted Orphan Drug Designation by US FDA for the Treatment of Cutaneous T-Cell Lymphoma TLC announced that product candidate TLC178 has been granted an orphan drug designation for the treatment of cutaneous T-cell lymphoma by the U.S. Food and Drug Administration (FDA). [Taiwan Liposome Company, Ltd.] Press Release Amgen announced that a Phase III study evaluating XGEVA® versus zoledronic acid met the primary endpoint of non-inferiority in delaying the time to first on-study skeletal-related event in patients with multiple myeloma. [Amgen Inc.] Press Release Northwestern Mutual Announces $900,000 in New Childhood Cancer Research Grants Northwestern Mutual, through its Foundation, announced the funding of six new grants supporting childhood cancer research. The causes of most childhood cancers are unknown, and for the most part these cancers cannot be prevented. The grants, distributed through Alex’s Lemonade Stand Foundation’s Young Investigator Program, are designed to support scientists early in their research careers. [Northwestern Mutual] Press Release | |
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POLICY NEWSReview Finds Misconduct in Events Surrounding WHO Fetal Growth Study For the first time in its 68-year history, the World Health Organization (WHO) has concluded that researchers are guilty of research misconduct. An independent review commissioned by WHO has found that “research ethics misconduct occurred” in a multimillion-dollar global study on fetal growth led by researchers at the University of Oxford in the United Kingdom. [ScienceInsider] Editorial Two Major California Research Institutes Will Merge One of the biggest nonprofit biomedical research outfits in the world is getting a new translational medicine research arm, aimed at speeding the conversion of basic research insights into novel medicines. Officials at the Scripps Research Institute announced that it will merge with the California Institute for Biomedical Research, which was launched in 2012 as a nonprofit version of a drug development company. [ScienceInsider] Editorial To Save Money, NSF Requires University Cost-Sharing for Rotators The National Science Foundation (NSF) has decided that universities should pay 10% of the salaries of faculty members working temporarily at the agency. NSF hopes the new policy will demonstrate its commitment to saving taxpayer dollars without alienating the academic community that it relies upon to stay on the cutting edge of basic science. [ScienceInsider] Editorial
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EVENTSNEW The 2nd Int’l Conference on Clinical and Experimental Hematology (ICCEH 2016) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Head of Laboratory – Cellular and Molecular Therapies (NHS Blood and Transplant) Research Technologist – Hematopoietic Product Development (STEMCELL Technologies) Postdoctoral Fellow – Proteomic Hematology (Lund University) Lecturer – Cancer Biology (NUI Galway) Scientist – In-Vitro Bone Marrow Toxicity (AstraZeneca) Assistant Member – Pediatric Oncology (Bone Marrow Transplant) Full Member Faculty Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Research Associate – Hematology (Editas Medicine) Faculty – Stem Cell Transplantation and Regenerative Medicine (Stanford University Medical School) 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 7.42 | Oct 25 2016