Hematopoiesis News 10.08 March 5, 2019 | |
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TOP STORYPerturbation of NCAM1 induced cell death or differentiation and sensitized leukemic blasts towards genotoxic agents in vitro and in vivo. Furthermore, Ncam1 was highly expressed in leukemic progenitor cells in a murine leukemia model, and genetic depletion of Ncam1 prolonged disease latency and significantly reduced leukemia-initiating cells upon serial transplantation. [Blood] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The Pluripotency Factor NANOG Controls Primitive Hematopoiesis and Directly Regulates Tal1 Using a dual transgene system for controlled expression at postimplantation stages, the authors found that Nanog blocked primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. [EMBO J] Full Article | Graphical Abstract Investigators showed that glucocorticoids enhanced erythrocyte production by slowing the rate of progression through a developmental continuum of transit-amplifying progenitors, permitting more cell divisions prior to terminal erythroid differentiation. [Dev Cell] Full Article | Press Release | Graphical Abstract Confocal microscopy analysis revealed an increase of localization of erythropoietin receptor to areas of membrane raft microdomains in response to erythropoietin stimulation in Ter119- erythroid progenitors, which was impaired in transmembrane protein 30A (Tmem30a) deficient cells. Consistently, knockdown of TMEM30A in human CD34+ cells also impaired erythropoiesis. [Haematologica] Full Article CUDC-907 induced DNA damage in acute myeloid leukemia cells while sparing normal hematopoietic cells. In addition, CUDC-907 treatment decreased leukemia progenitor cells in primary acute myeloid leukemia samples ex vivo, while also sparing normal hematopoietic progenitor cells. [Haematologica] Full Article PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells Scientists found that reducing protein arginine methyltransferase 5 (PRMT5) activity upregulated exon skipping and intron retention events that impaired gene expression. Consequently, loss of PRMT5 activity led to endogenous DNA damage that triggered p53 activation, induced apoptosis, and culminated in rapid HSC exhaustion, which was significantly delayed by p53 depletion. [Cell Rep] Full Article | Graphical Abstract Targeting RIPK1 in AML Cells Carrying FLT3-ITD Researchers started with murine myeloid progenitor 32D cells that ectopically expressed human fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (32D-FLT3-ITD) and found that RIPK1 was strongly upregulated in these cells. Subsequently, they showed that combinatorial treatment of 32D-FLT3-ITD cells with the SMAC mimetic BV6 and CD95L sensitized these cells towards apoptosis and necroptosis. [Int J Cancer] Abstract Stabilized expression of oxygen-insensitive hypoxia-inducible factors (HIFs) could not protect Lineage–Sca-1+c-kit+ (LSK) cells from oxidative stress-induced apoptosis at normoxia, neither could shRNA to HIF-1α inhibit the protective effects by hypoxia in LSK cells. [Antioxid Redox Signal] Abstract SOX6 Blocks the Proliferation of BCR-ABL1+ and JAK2V617F+ Leukemic Cells The inhibition of proliferation was the invariant outcome of SOX6 overexpression but it was achieved via two different cellular responses: terminal differentiation in erythroid-biased cells, irrespectively of their mutation, and apoptosis in megakaryocytic-primed and lymphoid cells. [Sci Rep] Full Article CLINICAL RESEARCHPatients with B-cell precursor acute lymphoblastic leukemia with late bone marrow relapses and low minimal residual disease at end of induction had favorable outcomes with chemotherapy without undergoing stem-cell transplantation. Patients with high minimal residual disease benefited from stem-cell transplantation, and targeted therapies might offer further improvements in outcomes for these patients. [Lancet Haematol] Full Article A retrospective study was conducted using the national registry data of 224 primary myelofibrosis patients to compare the outcomes of first allogeneic transplantation from HLA-matched related donor bone marrow (Rtd-BM), HLA-matched Rtd peripheral blood stem cells, HLA-matched unrelated donor (UR) BM, UR umbilical cord blood, and other hematopoietic stem cells. [Biol Blood Marrow Transplant] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSThe Role of TGFβ in Hematopoiesis and Myeloid Disorders Investigators provide an overview of the transforming growth factor-β (TGFβ) pathway, focusing on its role in hematopoiesis and impact on myeloid disorders. They discuss therapeutic interventions with promising results against myelodysplastic syndromes. [Leukemia] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSTetraphase Pharmaceuticals, Inc. announced it will present three posters on TP-2846, the company’s newly revealed pipeline candidate for acute myeloid leukemia. [Press release from Tetraphase Pharmaceuticals, Inc. discussing research to be presented at the 2019 American Association for Clinical Research (AACR) Annual Meeting, Atlanta] Press Release Aptose to Present New CG-806 and APTO-253 Data Aptose Biosciences Inc. announced that preclinical data for CG-806, its first-in-class, highly potent oral small molecule pan-FLT3/pan-BTK inhibitor, and APTO-253, its MYC inhibitor, will be presented in two separate posters. [Press release from Aptose Biosciences Inc. discussing research to be presented at the 2019 American Association for Clinical Research (AACR) Annual Meeting, Atlanta] Press Release Verastem, Inc. announced a poster highlighting clinical data from the Phase III DUO study evaluating COPIKTRA in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies was presented. [Press release from Verastem, Inc. discussing research presented at the 23rd Annual International Congress on Hematologic Malignancies (ICHM), Miami] Press Release | |
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INDUSTRY NEWSApellis Pharmaceuticals Inc. announced a novel, risk-sharing collaboration to support the development of APL-2 in hematologic indications with SFJ Pharmaceuticals. As part of this collaboration, SFJ and Apellis have entered into an agreement to support the development of APL-2 for the treatment of patients with paroxysmal nocturnal hemoglobinuria. [Apellis Pharmaceuticals Inc.] Press Release NantKwest, Inc. and ProMab Biotechnologies announced the establishment of a worldwide license to a B-Cell Maturation Antigen targeted antibody sequence for multiple myeloma along with an option for up to five undisclosed targeting sequences for exclusive use in the development of chimeric antigen receptor based NK cell therapies. [NantKwest, Inc.] Press Release TG Therapeutics, Inc. announced that the marginal zone lymphoma cohort of the UNITY-NHL Phase IIb pivotal trial evaluating umbralisib, the novel, once daily, PI3K delta inhibitor, met the primary endpoint of overall response rate (ORR) as determined by Independent Review Committee for all treated patients. The results met the company’s target guidance of 40-50% ORR. [TG Therapeutics, Inc.] Press Release Imbrium Therapeutics L.P. in conjunction with Mundipharma EDO GmbH announced that they have enrolled the first patient in the expansion stage of a Phase I/II clinical trial of tinostamustine, an investigational treatment, in patients with relapsed refractory hematologic malignancies in the US and Europe. [Imbrium Therapeutics L.P. (Business Wire)] Press Release CARsgen Therapeutics Receives IND Clearance for BCMA-CAR-T Cells from the NMPA CARsgen Therapeutics announced that one of its leading drug candidates, CT053 fully human BCMA (B-Cell Maturation Antigen)-CAR-T cell for the treatment of patients suffering from relapsed/refractory multiple myeloma, has received Investigational New Drug (IND) clearance from the National Medical Products Administration (NMPA). [CARsgen Therapeutics (PR Newswire Association LLC.)] Press Release Kura Oncology, Inc. announced that the FDA has cleared the company’s investigational new drug application for KO-539, a potent and selective small molecule inhibitor of the menin-mixed lineage leukemia (menin-MLL) protein-protein interaction. [Kura Oncology, Inc.] Press Release US FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis Celgene Corporation announced the FDA has accepted the company’s New Drug Application for fedratinib and granted a Priority Review. Fedratinib is a highly selective JAK2 inhibitor intended for the treatment of patients with myelofibrosis, a serious bone marrow disorder that disrupts the body’s normal production of blood cells. [Celgene Corporation] Press Release Aptose Biosciences and CrystalGenomics Announce Issuance of Australian Patent for CG-806 Aptose Biosciences Inc. that the Australian Patent Office has issued Australian Patent No. 2013371146 for CG-806, a first-in-class, highly potent oral small molecule being developed for acute myeloid leukemia, B cell and other hematologic malignancies. [Aptose Biosciences Inc.] Press Release Cell Medica announced that it has been awarded an $8.7 million research grant from the Cancer Prevention and Research Institute of Texas (CPRIT). The grant will support preclinical and clinical development of the company’s off-the-shelf chimeric antigen receptor-natural killer T cell (CAR-NKT) therapies to treat hematological and solid tumors. [Cell Medica] Press Release | |
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POLICY NEWSSecond Patient Free of HIV After Stem-Cell Therapy A person with HIV appears to be free of the virus after receiving a stem-cell transplant that replaced their white blood cells with HIV-resistant versions. The patient is only the second person ever reported to have been cleared of the virus using this method. But researchers warn that it is too early to say that they have been cured. [Nature News] Editorial China Creating National Medical Ethics Committee to Oversee High-Risk Clinical Trials A powerful new national medical ethics committee, which will approve all clinical trials involving high-risk biomedical technologies, is at the center of a regulatory shakeup Chinese authorities are planning in the aftermath of the widely condemned “CRISPR babies” experiment, STAT has learned. [STAT News] Editorial
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EVENTSNEW International Conference on Acute Lymphoblastic Leukemia Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation) NEW Postdoctoral Scientist – Lymphocyte/Leukemia Research (City of Hope) NEW Research Investigator – Lymphoma/Myeloma Research (MD Anderson Cancer Center) Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California at Davis) Postdoctoral Position – RNA Modifications, Hematopoiesis & Cancer (Lund University) Postdoctoral Research Fellow – Development of Lymphoid Cells (Lund University) 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) 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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