Figure 4.
Rescue of combined effects of AC220 and CB839 by αKG. (A-B) Oxygen consumption rate (OCR) in MV411 (A) and MOLM13 (B) cells treated with vehicle control, AC220 1 nM, CB839 100 nM, AC220 and CB839 combination, and AC220/CB839 combination + 4 mM dimethyl αKG measured using a Seahorse analyzer (for MV411 mean ± SEM, n = 3; for basal respiration: ** P = .0019 between AC220 and AC220+CB839, P = .018 between AC220 + CB839 and AC220 + CB839 + αKG; for maximal respiration: ***P = .0002 between AC220 and AC220 + CB839, P = .0224 between AC220 + CB839 and AC220 + CB839 + αKG, 2-way ANOVA with Bonferroni’s multiple comparisons; for MOLM13 cells: mean ± SEM, n = 3; for basal respiration: *P = .0298 between AC220 and AC220 + CB839, P = .0182 between AC220 + CB839 and AC220 + CB839 + αKG; for maximal respiration: *P = .02 between AC220 and AC220 + CB839, P = .0148 between AC220 + CB839 and AC220 + CB839 + αKG; 2-way ANOVA with Bonferroni’s multiple comparisons). (C-D) Relative cytoplasmic ROS levels of MV411 (C) and MOLM13 (D) cells treated as in panels A-B (for MV411: mean ± SEM, n = 5, * P = .0195, *** P = .0008; for MOLM13: mean ± SEM, n = 6, *P = .0345, ANOVA with Tukey’s multiple comparisons). (E-F) Apoptosis in MV411 (E) and MOLM13 (F) cells treated as in panels A-B (for MV411: mean ± SEM, n = 10, *P = .0158 between AC220 and AC220 + CB839 and *P = .0102 between AC220 + CB839 and AC220 + CB839 + αKG; for MOLM13: mean ± SEM, n = 9, *P = .0105 between AC220 and AC220+CB839, *P = .0120 between AC220 + CB839 and AC220 + CB839 + αKG, ANOVA with Tukey’s multiple comparisons).