A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia
Open accessAbstract
In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2). Tumor cells show little residual H3K27 trimethylation marks compared with controls. EZH2 is a component of the PRC2 Polycomb group protein complex, which is associated with DNA methyltransferases. Using next-generation sequencing, we identify alteration in gene expression levels of EZH2 and acquired mutations in PRC2-associated genes (DNMT3A and JARID2) in human adult T-ALL. Together, these studies document that deregulation of EZH2 and associated genes leads to the development of mouse, and likely human, T-ALL.
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High frequency of mutations in EZH2, EED, and SUZ12 are observed in patients with ETP-ALL.
“High frequency of mutations in EZH2, EED, and SUZ12 are observed in patients with early T cell precursor ALL (ETP-ALL) [154, 155].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [154]
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“…T-ALL, whether in the adult population (mutations: DNMT3A and JARID2; expression changes: EZH2 and KDM6B) (this study) or the childhood population (EZH2, EED, and SUZ12) (Zhang et al. 2012), argues for a more generalized deregulation of this Polycomb protein complex and associated genes in T-ALL.”
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- Authors
- Simon, C., Chagraoui, J., Krosl, J., Gendron, P., Wilhelm, B., Lemieux, S., Boucher, G., Chagnon, P., Drouin, S., Lambert, R., Rondeau, C., Bilodeau, A., Lavallée, S., Sauvageau, M., Hébert, J., & Sauvageau, G.
- Affiliations
- Institute for Research in Immunology and Cancer (CA)
- Hôpital Maisonneuve-Rosemont (CA)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-03-19
- Volume
- 26
- Issue
- 7
- Pages
- 651-656
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3323876
- OpenAlex
- W2154787712
- Cited by
- 264
- References
- 27
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 5 · 2023: 16 · 2022: 10 · 2021: 14 · 2020: 16 · 2019: 22 · 2018: 11 · 2017: 25 · 2016: 38 · 2015: 28 · 2014: 32 · 2013: 25 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- EZH2, adult T-cell acute lymphoblastic leukemia, polycomb repressive complex 2, H3K27me3, DNMT3A, JARID2, homozygous deletion, DNA methylation, gene expression dysregulation, mouse model
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Acute Disease, Animals, DNA-Binding Proteins, Humans, Mice, Inbred C57BL, Mice, Transgenic, Protein Binding, Histone-Lysine N-Methyltransferase, Repressor Proteins, Transcription Factors, Leukemia-Lymphoma, Adult T-Cell, Mice, Polycomb-Group Proteins, Polycomb Repressive Complex 2
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