FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia.

ABSTRACT: Understanding the regulation of N6-methyladenosine (m⁶A), the prominent internal modification in mRNA, fosters the development of potential therapeutic strategies for human cancers. While the m⁶A demethylases FTO and ALKBH5 are recognized for their crucial roles in various cancers, their impact on lymphoid leukemia remains uncertain. Using T cell acute lymphoblastic leukemia (T-ALL) as a model system, we identify FTO as a unique vulnerability in T cell leukemia. Knockout of FTO, but not ALKBH5, significantly suppresses leukemia initiation and progression. Mechanistic analysis reveals that FTO heightens ELK3 mRNA stability in an m⁶A-dependent manner. Elevated ELK3 in turn transcriptionally activates the expression of glycolytic genes. Ph

SUBMITTER: Huang H 

PROVIDER: S-EPMC12118595 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature