ArticleThe Journal of clinical investigation2013
Myelodysplastic syndromes are induced by histone methylation–altering ASXL1 mutations.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 172 citations in OpenAlex.
- The Disordered Region of ASXL1 Acts as an Auto-Regulator Through Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unleashed condensation by recurrent mutations of an epigenetic regulator promotes cancer.bioRxiv : the preprint server for biology · 2026Article
- The Immunological Consequences of Clonal Hematopoiesis in Heart Failure.Immunological reviews · 2026Review
- ASXL1 mutation-related clonal hematopoiesis and age-related diseases: clinical evidence and molecular insights.International journal of hematology · 2025Review
- Humanized mouse models in MDS.Cell death & disease · 2025Review
- Better Response and Prognosis of Venetoclax Plus Hypomethylating Agents Over Intensive Chemotherapy in Young Adults With Newly Diagnosed ASXL1-Mutated Acute Myeloid Leukemia.Cancer medicine · 2025Article
- Epigenetic dysregulation in acute myeloid leukemia.Seminars in hematology · 2025Review
- Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation.Blood advances · 2025Article
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
- The Molecular Pathology of Blood Cancer: A Comprehensive Review of Chromosome and Genetic Abnormalities and Their Clinical Utility.British journal of biomedical science · 2025Review
- Clonal hematopoiesis and hematological malignancy.The Journal of clinical investigation · 2024Review
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Human ASXL1-Mutant Hematopoiesis Is Driven by a Truncated Protein Associated with Aberrant Deubiquitination of H2AK119.Blood cancer discovery · 2024Article
- Precision Medicine Approaches in Acute Myeloid Leukemia with Adverse Genetics.International journal of molecular sciences · 2024Review
- Altered erythropoiesis via JAK2 and ASXL1 mutations in myeloproliferative neoplasms.Experimental hematology · 2024Article
- Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models.The Journal of clinical investigation · 2024Article
- Transcriptomic comparison of bone marrow CD34 + cells and peripheral blood neutrophils from ET patients with JAK2 or CALR mutations.BMC genomic data · 2023Article
- Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity.Nucleic acids research · 2023Article
- Epigenetic regulation by ASXL1 in myeloid malignancies.International journal of hematology · 2023Review
- Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation.JCI insight · 2023Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
Abstract
Recurrent mutations in the gene encoding additional sex combs-like 1 (ASXL1) are found in various hematologic malignancies and associated with poor prognosis. In particular, ASXL1 mutations are common in patients with hematologic malignancies associated with myelodysplasia, including myelodysplastic syndromes (MDSs), and chronic myelomonocytic leukemia. Although loss-of-function ASXL1 mutations promote myeloid transformation, a large subset of ASXL1 mutations is thought to result in stable truncation of ASXL1. Here we demonstrate that C-terminal–truncating Asxl1 mutations (ASXL1-MTs) inhibited myeloid differentiation and induced MDS-like disease in mice. ASXL1-MT mice displayed features of human-associated MDS, including multi-lineage myelodysplasia, pancytopenia, and occasional progression to overt leukemia. ASXL1-MT resulted in derepression of homeobox A9 (Hoxa9) and microRNA-125a (miR-125a) expression through inhibition of polycomb repressive complex 2–mediated (PRC2-mediated) methylation of histone H3K27. miR-125a reduced expression of C-type lectin domain family 5, member a (Clec5a), which is involved in myeloid differentiation. In addition, HOXA9 expression was high in MDS patients with ASXL1-MT, while CLEC5A expression was generally low. Thus, ASXL1-MT–induced MDS-like disease in mice is associated with derepression of Hoxa9 and miR-125a and with Clec5a dysregulation. Our data provide evidence for an axis of MDS pathogenesis that implicates both ASXL1 mutations and miR-125a as therapeutic targets in MDS.
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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.