Hematopoiesis News 10.47 December 3, 2019 | |
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TOP STORYHOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-Like Disease in Mice Investigators found that HOTTIP was aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuated leukemogenesis of transplanted mice, while reactivation of HOTTIP restored leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors showed that Hmces-deficient mice displayed normal hematopoiesis without global alterations in 5-hydroxymethylcytosine. HMCES specifically enabled DNA double-strand break repair through the microhomology-mediated alternative-end-joining pathway during class switch recombination (CSR) in B cells, and HMCES deficiency led to a significant defect in CSR. [Mol Cell] Abstract | Graphical Abstract Immunosuppression by Mutated Calreticulin Released From Malignant Cells Researchers used the retention using selective hooks assay to monitor the trafficking of C-terminally modified calreticulin (CALR). They found that exon-9-mutated CALR was released from cells in response to the biotin-mediated detachment from its ER-localized hook, in vitro and in vivo. Cellular CALR release was confirmed in suitable mouse models bearing exon-9-mutated hematopoietic systems or tumors. [Mol Cell] Abstract | Graphical Abstract Myeloid Lineage Enhancers Drive Oncogene Synergy in CEBPA/CSF3R Mutant Acute Myeloid Leukemia Scientists demonstrated that activating mutations in the granulocyte colony stimulating factor receptor (CSF3R) cooperated with loss of function mutations in the transcription factor CEBPA to promote acute leukemia development. The interaction between these distinct classes of mutations occured at the level of myeloid lineage enhancers where mutant CEBPA prevented activation of a subset of differentiation associated enhancers. [Nat Commun] Full Article Combining genomic, colony forming assay and xenograft studies, the authors detected the presence of juvenile myelomonocytic leukemia (JMML)-propagating cells that faithfully reproduced JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. [Leukemia] Full Article Liquid Biopsy for Minimal Residual Disease Detection in Leukemia Using a Portable Blast Cell Biochip Investigators described a robust system for the simultaneous detection and enrichment of rare blast cells. Enrichment of blast cells was achieved from blood with a one-step microfluidic blast cell biochip sorting system, without specific targeting of proteins by antibodies. [npj Precis Oncol] Full Article CLINICAL RESEARCHSingle-Cell Multiomic Analysis Identifies Regulatory Programs in Mixed-Phenotype Acute Leukemia Researchers established a normal epigenetic baseline for healthy blood development, which they then used to deconvolve aberrant molecular features within blood from patients with mixed-phenotype acute leukemia. Despite widespread epigenetic heterogeneity within the patient cohort, they observed common malignant signatures across patients as well as patient-specific regulatory features that were shared across phenotypic compartments of individual patients. [Nat Biotechnol] Abstract To determine the impact of age-related clonal hematopoiesis related mutations for development of fibrosis in primary myelofibrosis (PMF), the mutational status of cases with fibrotic progression from grade 0 to grade 2/3 as evidenced by follow-up bone marrow biopsies was compared with prefibrotic PMF samples without development of fibrosis. Frequent ARCH/CHIP-associated mutations demonstrable at presentation were not connected with fibrotic progression. [Leukemia] Abstract Using the CIBMTR registry, researchers report a time-trend analysis of 727 non-Hodgkin lymphoma patients undergoing the first allo-hematopoietic cell transplantation from 2000 to 2015 in the United States. Study cohorts were divided by time period: 2000–2005 vs. 2006–2010 vs. 2011–2015. Primary outcome was overall survival. Secondary outcomes included progression-free survival, relapse/progression, and non-relapse mortality. [Blood Cancer J] Full Article Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSExtramedullary Multiple Myeloma Despite improvement in survival for most patients with multiple myeloma over recent decades, outcomes were generally poor when extramedullary multiple myeloma develops. Understanding the molecular underpinnings leading to homing of plasma cells in ecosystems outside the bone marrow will be crucial for therapeutically manipulating the micro-environment and targeting key signaling pathways. [Leukemia] Abstract The Effect of Co-Occurring Lesions on Leukaemogenesis and Drug Response in T-ALL and ETP-ALL The authors outline the genomic alterations that occur in T cell acute lymphoblastic leukaemia (ALL) and early T cell precursor (ETP)-ALL and review studies highlighting the possible effects of co-occurring lesions on leukaemogenesis and drug response. [Br J Cancer] Abstract MicroRNAs in Graft-Versus-Host Disease: A Review of the Latest Data Investigators summarize the current knowledge on the involvement of small RNAs in the pathophysiology of this disease. They also review studies investigating the potential of miRNAs as biomarkers for early detection, follow-up, and prognosis of graft-versus-host disease. [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 NEWSAkari Therapeutics, Plc announced the design of a pivotal Phase III pediatric trial in HSCT-TMA following a FDA End-of-Phase II meeting. Akari also announces that, in another hematological condition, all six patients from the long-term Phase II PNH study who were transfusion dependent at entry are now transfusion independent on long-term treatment with nomacopan. [Akari Therapeutics, Plc] Press Release Rafael Pharmaceuticals, Inc. announced the expansion of its Phase II clinical trial of CPI-613® for patients with relapsed or refractory Burkitt’s lymphoma/leukemia. The clinical trial will begin enrolling patients at Massachusetts General Hospital in Boston starting this month. The trial is currently underway at Memorial Sloan Kettering Cancer Center in New York City and at City of Hope in Duarte, California. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release OSE Immunotherapeutics announced completion and positive results from the Phase study of OSE-127, a humanized monoclonal antibody with a differentiated mechanism of action as a full-antagonist of the CD127 receptor, the alpha chain of the interleukin-7 receptor. [OSE Immunotherapeutics] Press Release Seattle Genetics, Inc. announced that Health Canada has approved the supplemental New Drug Submission that expands the use of ADCETRIS in combination with CHP chemotherapy for the treatment of previously untreated adult patients with systemic anaplastic large cell lymphoma, peripheral T-cell lymphoma-not otherwise specified or angioimmunoblastic T-cell lymphoma, whose tumors express CD30. [Seattle Genetics, Inc.] Press Release | |
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POLICY NEWSCrack Down on Genomic Surveillance Concerns about the potential downsides of governments being able to interrogate people’s DNA have been voiced since the early 2000s by activist groups, such as the non-profit organization GeneWatch UK, and some geneticists. [Nature News] Editorial Elsevier Progresses in Open-Access Deal Making The scholarly publisher has announced several new licensing agreements in both Europe and the US, but some major academic groups are still without contracts and access to journals. [The Scientist] Editorial
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EVENTSNEW Keystone Symposia: Noncoding RNAs – Mechanism, Function and Therapies Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Oncogenic Events in Acute Lymphoblastic Leuemia (KU Leuven) Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.) Department Director – Hematopathology (University of Vermont) Postdoctoral Fellowships – Cancer Research (Harvard Medical School) Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences) 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) PhD Project – Physical Biology of Blood Stem Cells (University of York) Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer) 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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