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Tumour metabolism

The promoter becomes the suppressor

Somatic mutations in IDH1 or IDH2 are common in acute myeloid leukaemia (AML) and glioma, and result in a neomorphic enzyme that produces the metabolite R-2-hydroxyglutarate (R-2HG), which has been widely reported to have tumour-promoting activities. Su, Dong, Li et al. showed that R-2HG also has tumour suppressive effects in AML in vitro and in vivo, and in glioma cell lines. By inhibiting the RNA demethylase FTO, R-2HG increases N6-methyladenosine (m6A) of RNA, thus decreasing the stability of MYC and CEBPA mRNAs and allowing the observed inhibition of proliferation and survival. Cells that had high FTO were particularly sensitive to the anti-leukaemic effects of R-2HG, and those with high MYC were less sensitive.

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  1. 1

    Su, R. et al. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling. Cell 172, 90–105 (2018)

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Seton-Rogers, S. The promoter becomes the suppressor. Nat Rev Cancer 18, 66 (2018). https://doi.org/10.1038/nrc.2018.8

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