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Pulmonary Cell News| Hematopoiesis News 10.21 June 4, 2019 | |
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TOP STORYRadiation-Free Stem Cell Transplants, Gene Therapy May Be within Reach By tinkering with the components of the nutritive broth in which cells are grown, the specialized molecules used to support their growth and the physical conditions under which cells are cultivated, researchers have shown for the first time that it’s possible to coax hematopoietic stem cells from mice to renew themselves hundreds or even thousands of times within a period of just 28 days. [Press release from Stanford Medicine discussing online prepublication in Nature] Press Release | Abstract | Editorial | |
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PUBLICATIONS(Ranked by impact factor of the journal)Growth Dynamics in Naturally Progressing Chronic Lymphocytic Leukemia Scientists used the indolent growth dynamics of chronic lymphocytic leukemia (CLL) to analyze the growth rates and corresponding genomic patterns of leukemia cells from 107 patients with CLL, spanning decades-long disease courses. They found that CLL commonly demonstrated not only exponential expansion but also logistic growth, which was sigmoidal and reached a certain steady-state level. [Nature] Abstract | Press Release Safe Targeting of T Cell Acute Lymphoblastic Leukemia by Pathology-Specific NOTCH Inhibition The conditional knockout of presenilin-1 (Psen1) in developing T cells attenuated the development of a mutant NOTCH1-driven leukemia in mice in vivo but did not abrogate normal T cell development. Treatment of T cell acute lymphoblastic leukemia cell lines with the selective PSEN1 inhibitor MRK-560 effectively decreased mutant NOTCH1 processing and led to cell cycle arrest. [Sci Transl Med] Abstract | Press Release A Comprehensive Single Cell Transcriptional Landscape of Human Hematopoietic Progenitors Investigators provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovered a key missing branchpoint into basophils and expanded the understanding of the underlying structure of early adult human hematopoiesis. They also showed that this map had strong similarities in topology and gene expression to that found in mice. [Nat Commun] Full Article Scientists demonstrated the use of CRISPR/Cas9 and a short single-stranded oligonucleotide template to correct the sickle mutation in the β-globin gene in hematopoietic stem and progenitor cells from peripheral blood or bone marrow of patients with sickle cell disease, with 24.5 ± 7.6% efficiency without selection. [Nucleic Acids Res] Full Article | Press Release Using in vitro and ex vivo 3D-culture systems, ROR2 was shown to exert a pivotal role in the adhesion of cancer cells to the microenvironment. Genomic studies revealed that the pathways mostly deregulated by ROR2 overexpression were PI3K/AKT and mTOR. Treatment of cells with specific PI3K inhibitors already used in the clinic reduced myeloma cell adhesion to the bone marrow. [Leukemia] Abstract CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration Following Ionizing Radiation From an unbiased cytokine screen of murine marrow supernatants, researchers identified C-C motif chemokine ligand 5 (CCL5) as an endothelial cell-secreted hematopoietic growth factor. Following treatment with CCL5, hematopoietic regeneration was accelerated and survival was prolonged after radiation. [Stem Cell Reports] Full Article | Graphical Abstract CLINICAL RESEARCHIbrutinib and Venetoclax for First-Line Treatment of CLL Scientists conducted an investigator-initiated Phase II study of combined ibrutinib and venetoclax involving previously untreated high-risk and older patients with chronic lymphocytic leukemia (CLL). All patients had at least one of the following features: chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or an age of 65 years or older. [N Engl J Med] Abstract | Press Release A multicenter retrospective study was performed to explore a prognostic scoring index in order to identify a population who are least likely to benefit from allogeneic hematopoietic cell transplantation in patients with relapsed or refractory acute myeloid leukemia. [Leukemia] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSBeyond their canonical functions in healthy tissues, small extracellular vesicles (EVs) are strategically used by tumors to communicate with the cellular microenvironment and to establish a proper niche which would ultimately allow cancer cell proliferation, escape from the immune surveillance, and metastasis formation. The authors highlight the effects of hematological malignancy-derived small EVs on immune and stromal cells in the tumor microenvironment. [Cells] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSGenentech announced results from the pivotal Phase III CLL14 study in previously untreated chronic lymphocytic leukemia showing that Venclexta® plus Gazyva® met its primary endpoint of investigator-assessed progression-free survival. [Press release from Genentech discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the Phase III COLUMBA study, investigating a subcutaneously administered formulation of DARZALEX® co-formulated with recombinant human hyaluronidase PH20, in patients with relapsed/refractory multiple myeloma. [Press release from Janssen Global Services, LLC discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release The Janssen Pharmaceutical Companies of Johnson & Johnson announced long-term follow-up results from two pivotal Phase III studies of IMBRUVICA® in patients with CLL/small lymphocytic lymphoma, a type of non-Hodgkin lymphoma and the most common form of leukemia in adults [Press release from Janssen Global Services, LLC discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Kite announced results from the completed Phase I of the ZUMA-3 study evaluating KTE-X19, an investigational CD19 chimeric antigen receptor T cell therapy. ZUMA-3 is a single-arm Phase I/II study in adult patients with relapsed or refractory acute lymphoblastic leukemia. [Press release from Kite (Business Wire, Inc.) discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Celgene Corporation announced that data from the TRANSCEND CLL 004 and TRANSCEND NHL 001 trials studying the investigational anti-CD19 chimeric antigen receptor T-cell therapy lisocabtagene maraleucel (liso-cel) in patients with B-cell blood cancers were presented. [Press release from Celgene Corporation discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release AbbVie announced it will present more than 40 data updates across its oncology portfolio. The data presentations will span the company’s investigational and approved oncology portfolio medicines in more than 15 different blood and solid tumor cancers. [Press release from AbbVie, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago and research to be presented at the 24th European Hematology Association (EHA) Annual Congress, Amsterdam] Press Release Forty Seven, Inc. announced updated initial data from its Phase Ib clinical trial evaluating 5F9 as a monotherapy and in combination with azacitidine for the treatment of myelodysplastic syndrome and acute myeloid leukemia. [Press release from Forty Seven, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release New Data from Oncopeptides Phase I/II O-12-M1 Trial Evaluating Melflufen in RRMM Presented Oncopeptides AB announced new data presented from its Phase I/II O-12-M1 clinical study of lead candidate melflufen. The data demonstrate that melflufen may offer positive disease stabilization and favorable time to next treatment outcomes in heavily-pretreated patients with relapsed/refractory multiple myeloma (RRMM). [Press release from Oncopeptides AB discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Constellation Pharmaceuticals, Inc. announced the presentation of updated interim data from MANIFEST, the Company’s Phase II clinical trial of CPI-0610 in myelofibrosis. The interim data, which highlight the tolerability and potentially disease-modifying activity of CPI-0610, were presented in a poster. [Press release from Constellation Pharmaceuticals, Inc. discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Cyclerion Therapeutics to Present Data on Its Sickle Cell Disease Program Cyclerion Therapeutics, Inc. announced upcoming data presentations supporting its therapeutic approach in sickle cell disease (SCD). The company will also present an overview of olinciguat, its soluble guanylate cyclase stimulator under clinical investigation in the Phase I STRONG SCD study as a potential treatment for SCD. [Press release from Cyclerion Therapeutics, Inc. discussing research to be presented at the 24th European Hematology Association (EHA) Congress, Amsterdam and at the 13th Annual Sickle Cell Disease Research and Educational Symposium, Fort Lauderdale] Press Release | |
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INDUSTRY NEWSKite and Humanigen, Inc. announced the formation of a clinical collaboration to conduct a Phase I/II study of lenzilumab, an investigational anti-GM-CSF monoclonal antibody, with Yescarta® in patients with relapsed or refractory diffuse large B-cell lymphoma. [Humanigen, Inc.] Press Release Imara Announces FDA Fast Track Designation for IMR-687 for the Treatment of Sickle Cell Disease Imara, Inc. announced that the FDA has granted Fast Track designation to IMR-687, the company’s lead product candidate for the treatment of sickle cell disease. IMR-687 is currently being evaluated in a multi-national Phase IIa clinical trial in adult patients. [Imara, Inc.] Press Release NantKwest Inc. announced that the company’s t-haNK investigational new drug application has cleared FDA review, and the program has now transitioned to a first-in-human clinical trial targeting CD19 t-haNK in advanced B-cell lymphoma. [NantKwest Inc.] Press Release BioTheryX, Inc. announced that the FDA has cleared BioTheryX’s Investigational New Drug (IND) application for BTX-A51, an oral multi-kinase inhibitor, for the treatment of patients with relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome. [BioTheryX, Inc. (PR Newswire Association LLC)] Press Release bluebird bio, Inc. announced that the European Commission has granted conditional marketing authorization for ZYNTEGLOâ„¢, a gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia who do not have a β0/β0 genotype, for whom HSC transplantation is appropriate but a human leukocyte antigen-matched related HSC donor is not available. [bluebird bio, Inc.] Press Release Celgene Corporation and Acceleron Pharma Inc. announced that the FDA has accepted Celgene’s Biologics License Application for luspatercept, an investigational erythroid maturation agent, for the treatment of adult patients with very low to intermediate-risk myelodysplastic syndromes-associated anemia who have ring sideroblasts and require red blood cell (RBC) transfusions, and for the treatment of adult patients with beta-thalassemia-associated anemia who require RBC transfusions. [Celgene Corporation] Press Release Genmab A/S announced that the FDA granted a Priority Review for the supplemental Biologics License Application for the use of daratumumab in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are candidates for autologous stem cell transplant. [Genmab A/S] Press Release | |
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POLICY NEWSControversial US Bill Would Lift Supreme Court Ban on Patenting Human Genes A congressional proposal that would overturn a landmark US Supreme Court decision that barred the patenting of human genes and ease other restrictions on patenting software and biomedical inventions is drawing fierce criticism from some scientific societies and patient advocates. [ScienceInsider] Editorial China Urged to Abandon Plan to Sell Unproven Cell Therapies An international group of stem-cell researchers is urging China to cancel draft regulations that would permit some hospitals to sell therapies developed from patients’ own cells, without approval from the nation’s drug regulator. [Nature News] Editorial Brexit ‘May Bar UK Scientists From €100bn EU Research Fund’ The Horizon Europe program will fund €100bn in research projects, making it one of the largest science funds in the world. British researchers will be locked out unless the government negotiates an access deal in the coming months. [The Guardian] Editorial
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EVENTSNEW Cell Symposia: Gene and Cell Based Therapies: CRISPR, Stem Cells & Beyond Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Fellow – Hematology, Blood-Disorders & Stem Cell Biology (New York Blood Center) NEW Researcher – Clonal Hematopoiesis & Molecular Epidemiology (Uppsala University) Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Scientist – Hematopoietic Stem Cell Research (DKFZ / HI-STEM) Postdoctoral Scientist – Inflammatory Stress in the Bone Marrow (DKFZ / HI-STEM) Postdoctoral Fellow – Molecular Mechanisms of Myeloma (City of Hope) Assistant Professor – Lymphoma/Myeloma Research (The University of Texas MD Anderson Cancer Center) 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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