8-Cl-Ado and 8-NH₂-Ado synergize with venetoclax to target the methionine-MAT2A-SAM axis in acute myeloid leukemia.

ABSTRACT: Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular leve

SUBMITTER: Guo J 

PROVIDER: S-EPMC11147765 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature