ArticleThe Journal of clinical investigation2018
Ezh2 loss propagates hypermethylation at T cell differentiation-regulating genes to promote leukemic transformation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Profiling histone post-translational modifications to identify signatures of epigenetic drug response in T-cell acute lymphoblastic leukemia.Scientific reports · 2026Article
- Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Critical roles of IKAROS and HDAC1 in regulation of heterochromatin and tumor suppression in T-cell acute lymphoblastic leukemia.Leukemia · 2025Article
- Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Lsd1 safeguards T-cell development via suppressing endogenous retroelements and interferon responses.Life science alliance · 2023Article
- Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.International journal of molecular sciences · 2023Article
- Mechanisms of Polycomb group protein function in cancer.Cell research · 2022Review
- Adipocyte-mediated epigenomic instability in human T-ALL cells is cytotoxic and phenocopied by epigenetic-modifying drugs.Frontiers in cell and developmental biology · 2022Article
- EZH2 knockout in oral cavity basal epithelia causes more invasive squamous cell carcinomas.Carcinogenesis · 2021Article
- Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia.The Journal of clinical investigation · 2021Article
- Article
- EZH2 inhibition by tazemetostat: mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma.Future oncology (London, England) · 2021Article
- The Route of Early T Cell Development: Crosstalk between Epigenetic and Transcription Factors.Cells · 2021Review
- Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases.Frontiers in physiology · 2021Review
- Easy or Not-The Advances of EZH2 in Regulating T Cell Development, Differentiation, and Activation in Antitumor Immunity.Frontiers in immunology · 2021Review
- Early T-Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies.Frontiers in oncology · 2021Review
- Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies.International journal of molecular sciences · 2020Review
- Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia.Blood cancer discovery · 2020Article
- Advantages and Limitations of SNP Array in the Molecular Characterization of Pediatric T-Cell Acute Lymphoblastic Leukemia.Frontiers in oncology · 2020Article
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs. A large portion of PRC2 target genes acquired DNA hypermethylation of their promoters following reductions in H3K27me3 levels upon the loss of Ezh2, which included pivotal T cell differentiation-regulating genes. The reactivation of a set of regulators by a DNA-demethylating agent, but not the transduction of single regulator genes, effectively induced the differentiation of ETP-ALL cells. Thus, PRC2 protects key T cell developmental regulators from DNA hypermethylation in order to keep them primed for activation upon subsequent differentiation phases, while its insufficiency predisposes ETPs to leukemic transformation. These results revealed a previously unrecognized epigenetic switch in response to PRC2 dysfunction and provide the basis for specific rational epigenetic therapy for ETP-ALL with PRC2 insufficiency.
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