Hematopoiesis News 10.07 February 26, 2019 | |
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TOP STORYTargeting an RNA-Binding Protein Network in Acute Myeloid Leukemia Scientists uncovered a network of physically interacting RNA-binding proteins (RBPs) upregulated in acute myeloid leukemia (AML) and crucial for maintaining RNA splicing and AML survival. Genetic or pharmacologic targeting of one key member of the network, RBM39, repressed cassette exon inclusion and promoted intron retention within mRNAs encoding HOXA9 targets as well as in other RBPs preferentially required in AML. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)By single-cell RNA-sequencing, in vivo cell transfer experiments, and an assay for transposase-accessible chromatin sequencing using wild-type, IRF8-GFP chimera knock-in, or IRF8-knockout mice, the authors demonstrated that IRF8 regulated chromatin at the lymphoid-primed multipotent progenitor stage to induce early commitment towards dendritic cells. [Blood] Abstract A Stemness Screen Reveals C3orf54/INKA1 as a Promoter of Human Leukemia Stem Cell Latency Researchers interrogated functionally-validated datasets of leukemia stem cell-specific genes together with known protein interactors and selected 64 candidates for a competitive in vivo gain-of-function screen to identify genes that enhanced stemness in human cord blood hematopoietic stem and progenitor cells. [Blood] Abstract Genetic Programming of Macrophages Generates an In Vitro Model for the Human Erythroid Island Niche The erythroblastic island-like macrophages increased the production of mature, enucleated erythroid cells from umbilical cord blood derived CD34+ hematopoietic progenitor cells and induced pluripotent stem cells; this enhanced production was partially retained even when the contact between progenitor cells and macrophages was inhibited, suggesting that KLF1-induced secreted proteins may be involved in this enhancement. [Nat Commun] Full Article TET2 Binding to Enhancers Facilitates Transcription Factor Recruitment in Hematopoietic Cells The authors found that deletion of Tet2 in native hematopoiesis as well as fully transformed Acute Myeloid Leukemia (AML) resulted in changes in transcription factor (TF) activity within these regions, and they provide evidence that loss of TET2 led to the attenuation of chromatin binding of members of the basic helix-loop-helix TF family. [Genome Res] Abstract MicroRNA-127-3p Controls Murine Hematopoietic Stem Cell Maintenance by Limiting Differentiation miR-127-3p was strongly stem cell-specific, being quickly down-regulated upon differentiation and not re-expressed further downstream in the bone marrow hematopoietic hierarchy. Inhibition of miR-127-3p function in lineage-negative cells, achieved through a lentiviral-sponge vector, led to severe stem cell depletion as assessed with serial transplantation assays. [Haematologica] Abstract | Full Article Bone Marrow Adipose Tissue-Derived Stem Cell Factor Mediates Metabolic Regulation of Hematopoiesis Investigators found that both Adipoq-Kitl KO and Osx1-Kitl KO mice lost hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. [Haematologica] Abstract | Full Article Scientists showed that lymphoid-biased hematopoietic stem cells (Ly-HSCs) did not decline in number with age. Old Ly-HSCs exhibited changes in gene expression and a myeloid-biased genetic profile, but they demonstrated that they retained normal lymphoid potential when removed from the old in vivo environment. [Stem Cell Reports] Full Article | Graphical Abstract CLINICAL RESEARCHInvestigators examined the effects of carfilzomib-dexamethasone versus bortezomib-dexamethasone on health-related quality of life in relapsed/refractory multiple myeloma patients from the ENDEAVOR study. [Blood Cancer J] Full Article The three-year overall survival rate of the 41 primary induction failure (PIF) patients was 19.0%. High leucocyte count, M7 morphology, and unfavorable genetic aberrations, such as FLT3-internal tandem duplication, NUP98-NSD1 and high MECOM or PRDM16 expression, were risk factors for PIF. [Br J Haematol] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSEmerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation The authors argue for the importance of system-wide evaluation of changes in myelopoiesis and discuss how even after the resolution of inflammation, long-lasting alterations in myelopoiesis may play a role in innate immune memory or trained immunity. [Immunity] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSAgios Pharmaceuticals, Inc. presented updated data from a Phase I study evaluating ivosidenib in combination with azacitidine in newly diagnosed isocitrate dehydrogenase-1 (IDH1) mutant AML patients. [Press release from Agios Pharmaceuticals, Inc. discussing research presented at the 17th International Symposium on Acute Leukemias, Munich] Press Release Magenta Therapeutics announced that the company highlighted preclinical research on its targeted conditioning programs in four presentations and posters. [Press release from Magenta Therapeutics discussing research presented at the Transplant and Cellular Therapy (TCT) Annual Meeting, Houston] Press Release Orchard Therapeutics presented two-year follow-up data in 20 patients from the registrational trial evaluating OTL-101, an autologous, ex vivo, hematopoietic stem cell gene therapy for the treatment of severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). [Press release from Orchard Therapeutics discussing research presented at the 2019 Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR, Houston] Press Release | |
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INDUSTRY NEWSGenmab Announces Positive Topline Results in Phase III COLUMBA Study of Subcutaneous Daratumumab The results showed that subcutaneous administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 is non-inferior to IV administration of daratumumab with regard to the co-primary end points of overall response rate and Maximum Trough concentration of daratumumab on day one of the third treatment cycle. [Genmab A/S] Press Release Cellectar Biosciences, Inc. announced additional positive top-line results from its ongoing Phase II clinical study of CLR 131, the company’s lead product candidate. In the relapse refractory multiple myeloma cohort, CLR 131 achieved a 30% overall response rate in the first 10 evaluable patients. [Cellectar Biosciences, Inc.] Press Release BeiGene, Ltd. announced that the first patient was dosed in a global Phase II trial of zanubrutinib, an investigational inhibitor of Bruton’s tyrosine kinase, in patients with relapsed or refractory marginal zone lymphoma, which BeiGene refers to as the MAGNOLIA trial. [BeiGene, Ltd.] Press Release ADC Therapeutics announced that the first patient has been dosed in a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-402 in combination with Pharmacyclics LLC’s ibrutinib in patients with advanced diffuse large B-cell lymphoma or mantle cell lymphoma. [ADC Therapeutics] Press Release Xencor Announces Partial Clinical Hold on Phase I Study of XmAb14045 Xencor, Inc. announced that the FDA has placed a partial clinical hold on its Phase I study of XmAb14045, a CD123 x CD3 bispecific antibody molecule being evaluated in patients with relapsed or refractory acute myeloid leukemia and other CD123-expressing hematologic malignancies. [Xencor, Inc.] Press Release Agios Pharmaceuticals, Inc. announced that the FDA has accepted the company’s supplemental New Drug Application for TIBSOVO® for the treatment of patients with newly diagnosed acute myeloid leukemia with an isocitrate dehydrogenase 1 mutation who are not eligible for standard therapy. [Agios Pharmaceuticals, Inc.] Press Release Aptose Biosciences Submits IND Application for CG-806 Aptose Biosciences Inc. announced that it has submitted an Investigational New Drug (IND) application for CG-806 to the FDA requesting approval to initiate its Phase I clinical trial program. [Aptose Biosciences Inc.] Press Release City of Hope announced that it has received its third lymphoma SPORE grant from the National Cancer Institute (NCI), one of four current NCI-supported lymphoma SPOREs. The grant covers a five-year period and totals $12.5 million. [City of Hope] Press Release Blood Disorder Research Receives 2.5 Million from the NIH Feinstein Institute for Medical Research Associate Professor and anemia expert Lionel Blanc, PhD, received a five-year, $2.5 million National Institutes of Health (NIH) grant to study improved treatment for erythropoietic disorders, including Diamond Blackfan anemia. [Feinstein Institute for Medical Research] Press Release | |
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POLICY NEWSOpen-Access Pioneer Randy Schekman on Plan S and Disrupting Scientific Publishing Nobel laureate Randy Schekman shook up the publishing industry when he launched the open-access journal eLife in 2012. Armed with millions in funding from three of the world’s largest private biomedical charities — the Wellcome Trust, the Max Planck Society and the Howard Hughes Medical Institute — Schekman designed the journal to compete with publishing powerhouses such as Nature, Science and Cell. [Nature News] Editorial Cities and states around the corner and around the country have angled for years to set themselves up as the next Kendall Square, hoping to import some of the magic of Boston’s biotech hub and its job-creating economic engine. Increasingly, foreign governments are pushing for the same. [STAT News] Editorial
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EVENTSNEW ISCT 2019 Annual Scientific Meeting Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Position – RNA Modifications, Hematopoiesis & Cancer (Lund University) Postdoctoral Research Fellow – Development of Lymphoid Cells (Lund University) Chair – Microbiology and Immunology (Indiana University School of Medicine) 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 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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