Hematopoiesis News 11.04 February 4, 2020 | |
| |
TOP STORYA Central Role of IKK2 and TPL2 in JNK Activation and Viral B-Cell Transformation Investigators identified a novel and critical function of IκB kinase 2 (IKK2) and its co-factor NEMO in the activation of oncogenic c-Jun N-terminal kinase (JNK) signaling, induced by the latent membrane protein 1 (LMP1) of Epstein-Barr virus. Independent of its kinase activity, the TGFβ-activated kinase 1 mediates LMP1 signaling complex formation, NEMO ubiquitination and subsequent IKK2 activation. [Nat Commun] Full Article | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Researchers identified a consistent regulatory program starting with a sharp decrease of NF-κB binding in chronic lymphocytic leukemia (CLL) cells, which was followed by reduced activity of lineage-defining transcription factors, erosion of CLL cell identity, and acquisition of a quiescence-like gene signature. [Nat Commun] Full Article Loss of Kat2a Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells Through combined chromatin profiling and single-cell transcriptomics of a conditional knockout mouse, the authors demonstrated that Kat2a contributed to leukemia propagation through preservation of leukemia stem-like cells. Kat2a loss impacted transcription factor binding and reduces transcriptional burst frequency in a subset of gene promoters, generating enhanced variability of transcript levels. [eLife] Abstract Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a fetal factor that undergoes a transcriptional switch consistent with the transition from fetal hemoglobin to adult hemoglobin. Lentivirus delivery of IGF2BP1 to CD34+ cells of healthy adult donors reversed hemoglobin production toward the fetal type in culture-differentiated erythroid cells. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract The authors found that overexpression of DNMT3A mutants in KMT2A-histone-lysine N-methyltransferase 2A-partial tandem duplication (PTD)-positive EOL-1 cells augmented cell proliferation and clonogenicity. Serial colony replating assays indicated that DNMT3A-mutants increased the self-renewal ability of Kmt2a-PTD-expressing mouse bone marrow cells with immature morphology. [Oncogenesis] Full Article Investigators employed optical clearing, confocal microscopy and nearest neighbor analysis to determine the spatial distribution of CD34+ hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) in a translationally relevant rhesus macaque model. Immunofluorescent analysis revealed that femoral BM adipocytes were associated with the branches of vascular sinusoids, with half of HSPCs localizing in close proximity of the nearest BM adipocyte. [Bone] Abstract The authors employed cyclosporine H for lentivirus transduction of murine hematopoietic stem cells and defined hematopoietic progenitors, confirming previous findings in more specific subsets of primitive hematopoietic cells. The data confirmed increased efficiencies, in agreement with the published data. [Sci Rep] Full Article CLINICAL RESEARCHScientists tested whether the MAGIC algorithm probability could identify patients whose risk for relapse is higher than their risk for severe graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The multi-center study population was divided into two cohorts: historical and current with similar NRM, relapse, and survival. [Leukemia] Abstract The authors retrospectively analyzed in a population of 670 children receiving allogeneic hematopoietic stem cell transplantation for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation and busulfan, as part of the preparative regimen. [Bone Marrow Transplant] Abstract Researchers retrospectively analyzed the contributions of lineage-sorted donor cell chimerism (sDCC) and quantitative PCR (qPCR) targeting disease-specific genetic rearrangements to detect minimal residual/relapsing disease and predict impending relapse in 94 adult adult lymphoblastic leukemia patients after stem cell transplantation. With a median follow-up of surviving patients of 3.3 years, qPCR and/or sDCC measurements turned positive in 38 patients. [Bone Marrow Transplant] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
| |
REVIEWSPersonal Tumor Antigens in Blood Malignancies: Genomics-Directed Identification and Targeting The authors review the advances in systematic identification of minor histocompatibility antigens and neoantigens arising from personal somatic alterations or recurrent driver mutations. These exciting efforts pave the path for the implementation of personalized combinatorial cancer therapy. [J Clin Invest] Abstract Immunotherapy for the Treatment of Acute Lymphoblastic Leukemia The biologic and clinical contexts in which immunotherapies have advanced the treatment of acute lymphoblastic leukemia (ALL) confer optimism that more patients will achieve durable remissions. Immunotherapy treatments in ALL will expand through rationally targeted approaches alongside advances in CAR T cell therapy design and clinical experience. [Curr Oncol Rep] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
INDUSTRY NEWSVerastem, Inc. announced that its partner CSPC Pharmaceutical Group Limited has dosed the first patient in a pivotal Chinese bridging study evaluating COPIKTRA® in patients with relapsed or refractory follicular lymphoma. [Verastem Oncology, Inc.] Press Release Moleculin Announces Successful Completion of US Phase I AML Trial of Annamycin Moleculin Biotech, Inc. announced that its open label, single arm US Phase I trial met its primary objective of demonstrating the safety of Liposomal Annamycin in treating relapsed or refractory acute myeloid leukemia. [Moleculin Biotech, Inc.] Press Release AbbVie announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has granted a positive opinion for VENCLYXTO® in combination with obinutuzumab for the treatment of patients with chronic lymphocytic leukemia who were previously untreated. [AbbVie] Press Release Children’s Hospital Los Angeles (CHLA) announced today that the Margie and Robert E. Petersen Foundation has contributed $25 million to establish an endowment supporting three of the hospital’s signature programs: the Cancer and Blood Disease Institute, the Vision Center and Inpatient Rehabilitation Services. [Children’s Hospital Los Angeles] Press Release | |
| |
POLICY NEWSWhy Did a Chinese University Hire Charles Lieber to Do Battery Research? Among the ongoing mysteries surrounding last week’s arrest of Harvard University nanoscientist Charles Lieber is the precise nature of the research program Lieber was conducting in his cooperation with Chinese researchers. [ScienceInsider] Editorial Cash from Cannabis Companies Creates Conflicted Researchers Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial
| |
EVENTSNEW Tumor Metabolism Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESScientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.) Postdoctoral Fellow – Hereditary and Childhood Tumors (The University of British Columbia) Postdoctoral Fellowship – Personalized Cancer Treatments (MGH Cancer Center) Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research) Faculty Position – Cancer Epidemiology (MD Anderson Cancer Center) Research Fellow – Hematology & Blood Disorders (New York Blood Center) Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine) Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine) Associate/Professor – Hematology & Oncology (UC Davis School of Medicine) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
| |
Have we missed an important article or publication in Hematopoiesis News? Click here to submit! Comments or suggestions? Submit your feedback here. | |
|