| First Author | Gioulbasani M | Year | 2024 |
| Journal | Commun Biol | Volume | 7 |
| Issue | 1 | Pages | 1606 |
| PubMed ID | 39627458 | Mgi Jnum | J:359295 |
| Mgi Id | MGI:7785773 | Doi | 10.1038/s42003-024-07312-0 |
| Citation | Gioulbasani M, et al. (2024) Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability in mice. Commun Biol 7(1):1606 |
| abstractText | Ten eleven translocation (TET) proteins are tumor suppressors that through their catalytic activity oxidize 5-methylcytosine to 5-hydroxymethylcytosine, to promote DNA demethylation and to regulate gene expression. Notably, TET2 is one of the most frequently mutated genes in hematological malignancies, including T cell lymphomas. However, murine models with deletion of TET2 do not exhibit T cell expansion, presumably due to redundancy with other members of the TET family of proteins. In order to gain insight on the TET mediated molecular events that safeguard T cells from aberrant proliferation we performed serial adoptive transfers of murine CD4 T cells that lack concomitantly TET2 and TET3 to fully immunocompetent congenic mice. Here we show a progressive acquisition of malignant traits upon loss of TET2 and TET3 that is characterized by loss of genomic integrity, acquisition of aneuploidy and upregulation of the protooncogene Myc. |
