ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia.

ABSTRACT: Metabolic reprogramming is a common feature of many human cancers, including acute myeloid leukemia (AML). However, the upstream regulators that promote AML metabolic reprogramming and the benefits conferred to leukemia cells by these metabolic changes remain largely unknown. We report that the transcription factor ATF3 coordinates serine and nucleotide metabolism to maintain cell cycling, survival, and the differentiation blockade in AML. Analysis of mouse and human AML models demonstrate that ATF3 directly activates the transcription of genes encoding key enzymatic regulators of serine synthesis, one-carbon metabolism, and de novo purine and pyrimidine synthesis. Total steady-state polar metabolite and heavy isotope tracing analyses show that ATF3 inhibition reduces de novo serine synthe

SUBMITTER: Di Marcantonio D 

PROVIDER: S-EPMC8452149 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature