Inhibition of c-KITmut kinase causes DSB repair defects and restores sensitivity of AML1-ETO–positiveAML cells to the PARPi olaparib. (A) Tyrosine-phosphorylated proteins (pY) and indicated DSB repair proteins were detected by western blot in total cell lysates (left panel) and nuclear cell lysates (right panel) from Kasumi-1 cells treated (designated by “A”) or not (-) with avapritinib. Actin and lamin served as loading controls. (B) HR, D-NHEJ, and Alt-NHEJ activities in Kasumi-1 cells treated (designated by “A”) or not (-) with avapritinib. Results represent mean percentage ± standard deviation (SD) of GFP⁺ cells in DsRed⁺ population from 3 experiments. *P < .001, Student t test. (C) Kasumi-1 cells were left untreated (-) or treated with 5-μM avapritinib (designated by “A”), 5-μM olaparib (O), or avapritinib + olaparib (AO). Mean ± SD number of colonies from 3 experiments. *P < .05, Mann-Whitney rank sum test. (D) Clonogenic potential of Lin⁻CD34⁺ cells from 3 AML patients harboring AML1-ETO + c-KITmut (AEK), 3 AML1-ETO (AE)–positive AMLs, and from 3 healthy donors (N) treated with the indicated concentrations of olaparib (O) or 5-μM avapritinib + olaparib (AO). Mean percentage ± SD of colonies compared with untreated counterparts.