Highlight
- FLT3-ITD acute myeloid leukemia (AML) often develops resistance to FLT3 tyrosine kinase inhibitors (TKIs), necessitating novel targets to overcome drug tolerance.
- The mitochondrial complex I subunit NDUFS2 is identified as a key mediator of tolerance to FLT3 TKI therapy in FLT3-ITD AML.
- Targeting NDUFS2 genetically or pharmacologically decreases mitochondrial respiratory function, promoting apoptosis and restoring FLT3 inhibitor sensitivity.
- Preclinical models show that combining FLT3 inhibitors with mitochondrial complex I inhibition reduces leukemia burden without overt toxicity.
Study Background
