Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia

NOTCH1-mutated T-ALL is a feasible target for OxPhos inhibitors owing to its significantly upregulated mitochondrial machinery. Mitochondrial OxPhos can be effectively targeted by the novel inhibitor of mitochondrial complex I IACS-010759, which demonstrated preclinical activity in NOTCH1-mutated T-ALL We used RNAseq to compare gene expression of ICAS, CB839, ICAS_CB839 and Vehicle treated samples in Leukemia cell lines.