Researchers have announced new discoveries about the TET2 gene, which is involved in a large proportion of myeloid malignancies.
Professor Mingjiang Xu, who has led a new study on the gene, says the findings now open a door to targeted treatments and prevention.
About 30% of patients with myeloid disease have mutations in the gene, which has a tumour suppressing function, the researchers say.
However, the mechanism of TET2's role in blood cancers was not clear. Previous researchers had been focussed on TET2's action on DNA.
But this latest study, reported in Nature, points to the role of TET2's enzymatic activity on RNA, showing that the gene can modify chromatin-associated RNA, leading to changes in gene expression.
This can lead to the activation and growth of blood cancer cells, according to the researchers. They proposed the protein MBD6 as a "great therapeutic target" for treating cancers with the TET2 mutation.
Professor Xu, of The University of Texas Health Science Center at San Antonio, said the findings could be "transformational" for patients with disease associated with TET2 mutation.
Professor Xu said: "One thing that surprised us was how powerful this pathway is on TET2-mediated gene expression. It is a quantum structure change mediated by this pathway."
Source: Zou Z, Dou X, Li Y, Zhang Z, Wang J, Gao B, Xiao Y, Wang Y, Zhao L, Sun C, Liu Q, Yu X, Wang H, Hong J, Dai Q, Yang FC, Xu M, He C. (2024) “RNA M⁵C oxidation by TET2 regulates chromatin state and leukaemogenesis.” Nature, 2 October 2024, doi: 10.1038/s41586-024-07969-x.
Link: https://www.nature.com/articles/s41586-024-07969-x
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