ArticleScientific reports2018
ASXL1 and SETBP1 mutations promote leukaemogenesis by repressing TGFβ pathway genes through histone deacetylation.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 36 citations in OpenAlex.
- Overexpression of the TGF-β target CCN2 in megakaryocytes: a common feature of MDS with mutated SF3B1 : Uncovering novelinsights into the bone marrow microenvironment in MDS.Virchows Archiv : an international journal of pathology · 2026Article
- Machine Learning-Based Predictive Modeling Maximizes the Efficacy of mTOR/p53 Co-Targeting Therapy Against AML.Cancer science · 2025Article
- Integrated analysis of histone modification features in clear cell renal cancer for risk stratification and therapeutic prediction.Translational oncology · 2024Article
- Modeling and therapeutic targeting of t(8;21) AML with/without TP53 deficiency.International journal of hematology · 2024Article
- Prognostic significance of ASXL1 mutations in acute myeloid leukemia: A systematic review and meta-analysis.Caspian journal of internal medicine · 2024Review
- Hyperactive Natural Killer cells in Rag2 knockout mice inhibit the development of acute myeloid leukemia.Communications biology · 2023Article
- Article
- The impact of SETBP1 mutations in neurological diseases and cancer.Genes to cells : devoted to molecular & cellular mechanisms · 2023Review
- Proposals for Clinical Trials in Chronic Myelomonocytic Leukemia.Current treatment options in oncology · 2023Review
- Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study.Journal of cancer research and clinical oncology · 2023Article
- Clonal hematopoiesis and bone marrow inflammation.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Role of ASXL1 in hematopoiesis and myeloid diseases.Experimental hematology · 2022Review
- CHIP-associated mutant ASXL1 in blood cells promotes solid tumor progression.Cancer science · 2022Article
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- Targeting low-risk myelodysplastic syndrome with novel therapeutic strategies.Trends in molecular medicine · 2021Review
- Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome.International journal of molecular sciences · 2021Review
- Review
- A Broad Overview of Signaling inCancers · 2021Review
- Clinical implication and prognostic significance of FLT3-ITD and ASXL1 mutations in Egyptian AML patients: A single-center study.Cancer biomarkers : section A of Disease markers · 2021Article
- Molecular Regulation of the Polycomb Repressive-Deubiquitinase.International journal of molecular sciences · 2020Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in ASXL1 and SETBP1 genes have been frequently detected and often coexist in myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). We previously showed that coexpression of mutant ASXL1 and SETBP1 in hematopoietic progenitor cells induced downregulation of TGFβ pathway genes and promoted the development of MDS/AML in a mouse model of bone marrow transplantation. However, whether the repression of TGFβ pathway in fact contributes to leukaemogenesis remains unclear. Moreover, mechanisms for the repression of TGFβ pathway genes in ASXL1/SETBP1-mutated MDS/AML cells have not been fully understood. In this study, we showed that expression of a constitutively active TGFβ type I receptor (ALK5-TD) inhibited leukaemic proliferation of MDS/AML cells expressing mutant ASXL1/SETBP1. We also found aberrantly reduced acetylation of several lysine residues on histone H3 and H4 around the promoter regions of multiple TGFβ pathway genes. The histone deacetylase (HDAC) inhibitor vorinostat reversed histone acetylation at these promoter regions, and induced transcriptional derepression of the TGFβ pathway genes. Furthermore, vorinostat showed robust growth-inhibitory effect in cells expressing mutant ASXL1, whereas it showed only a marginal effect in normal bone marrow cells. These data indicate that HDAC inhibitors will be promising therapeutic drugs for MDS and AML with ASXL1 and SETBP1 mutations.
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