Increased BIM and decreased MCL-1 expression underlies synergistic cell death in FLT3-mutant cells treated with the combination of quizartinib and dexamethasone. A representative immunoblot (A) and quantification of replicate experiments (B-D) (n = 4) showing expression of BCL-2 family proteins following treatment with the indicated drugs (100 nM quizartinib, 50 µM dexamethasone) for 48 hours. Statistical significance is based on comparison of each treatment to DMSO. A representative immunoblot (E) and quantification of replicate experiments (F) (n = 2) showing the ratio of BIM to MCL-1 in GR-knockout MV4-11 cells following treatment with the indicated drugs (100 nM quizartinib and 50 µM dexamethasone) for 48 hours. (G) Immunoblot showing abrogation of phosphorylated AKT in MV4-11 cells after treatment with the indicated drugs (100 nM quizartinib and 50 µM dexamethasone) for 48 hours. (H) A representative immunoblot (n = 2) showing rescue of quizartinib and combination treatment-induced MCL-1 degradation with either bortezomib (Bort) (10 nM) or GSK inhibitor CHIR99021 (CHIR) (10 µM) cotreatment in MV4-11 cells for 18 hours.