ArticleLeukemia2019
ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Beyond the JAK2 mutation: The inflammasome, clonal stability, and the thrombotic niche in myeloproliferative neoplasms.Clinical and experimental medicine · 2026Review
- ASXL1 mutation-related clonal hematopoiesis and age-related diseases: clinical evidence and molecular insights.International journal of hematology · 2025Review
- Genetic and immunologic features associated with thrombocytopenia progression and poor prognosis in patients with myelofibrosis.Frontiers in medicine · 2024Article
- Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.Nature medicine · 2023Article
- Stage-specific dual function: EZH2 regulates human erythropoiesis by eliciting histone and non-histone methylation.Haematologica · 2023Article
- Understanding the Continuum between High-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- Novel Molecular Insights into Leukemic Evolution of Myeloproliferative Neoplasms: A Single Cell Perspective.International journal of molecular sciences · 2022Review
- Clinical Features, Gene Alterations, and Outcomes in Prefibrotic and Overt Primary and Secondary Myelofibrotic Patients.Cancers · 2022Article
- Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing.Life (Basel, Switzerland) · 2021Review
- Philadelphia-Negative MPN: A Molecular Journey, from Hematopoietic Stem Cell to Clinical Features.Medicina (Kaunas, Lithuania) · 2021Review
- Molecular pathogenesis of the myeloproliferative neoplasms.Journal of hematology & oncology · 2021Review
- Article
- Philadelphia-Negative Myeloproliferative Neoplasms: Laboratory Workup in the Era of Next-Generation Sequencing.Current hematologic malignancy reports · 2019Review
- Relationship between disease biology and clinical phenotype in myeloproliferative neoplasms.HemaSphere · 2019Article
- The ruxolitinib effect: understanding how molecular pathogenesis and epigenetic dysregulation impact therapeutic efficacy in myeloproliferative neoplasms.Journal of translational medicine · 2018Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary myelofibrosis (PMF) is a hematopoietic stem cell (HSC) disease, characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. PMF samples carry several mutations, but their cell origin and hierarchy in regulating the different waves of clonal and aberrant myeloproliferation from the prime HSC compartment is poorly understood. Genotyping of >2000 colonies from CD133+HSC and progenitors from PMF patients confirmed the complex genetic heterogeneity within the neoplastic population. Notably, mutations in chromatin regulators ASXL1 and/or EZH2 were identified as the first genetic lesions, preceding both JAK2-V617F and CALR mutations, and are thus drivers of clonal myelopoiesis in a PMF subset. HSC from PMF patients with double ASXL1/EZH2 mutations exhibited significantly higher engraftment in immunodeficient mice than those from patients without histone modifier mutations. EZH2 mutations correlate with aberrant erythropoiesis in PMF patients, exemplified by impaired maturation and cell cycle arrest of erythroid progenitors. These data underscore the importance of post-transcriptional modifiers of histones in neoplastic stem cells, whose clonal growth sustains aberrant myelopoiesis and expansion of pre-leukemic clones in PMF.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.