D-2-HG Inhibits IDH1mut Glioma Growth via FTO Inhibition and Resultant m6A Hypermethylation.
Sean Thomas PiankaTie LiTerry J PrinsBlaine S C EldredBryan M KevanHaowen LiangSerendipity Zapanta RinonosHarley I KornblumDavid A NathansonMatteo PellegriniLinda M LiauPhioanh Leia NghiemphuTimothy F CloughesyAlbert LaiPublished in: Cancer research communications (2024)
We show that IDH1mut-generated D-2-HG can reduce glioma growth via inhibition of the m6A demethylase, FTO. FTO inhibition represents a potential therapeutic target for IDH1wt gliomas and possibly in conjunction with IDH1mut inhibitors for the treatment of IDH1mut glioma. Future studies are necessary to demonstrate the role of ATF5 downregulation in the indolent phenotype of IDH1mut gliomas, as well as to identify other involved gene transcripts deregulated by m6A hypermethylation.