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. Author manuscript; available in PMC: 2021 Dec 14.
Published in final edited form as: Cancer Cell. 2020 Nov 19;38(6):872–890.e6. doi: 10.1016/j.ccell.2020.10.010

Figure 5: Mitochondrial sensitivities to BH3 peptides reveal basis for synergy between BH3 mimetics.

Figure 5:

(A-B) Heat map of delta priming response in AML cell lines after treatment with (A) 5nM venetoclax and (B) 50nM S63845 for 16 h, determined by dynamic BH3 profiling (n=3).

(C-D) Delta priming kinetics of MOLM-13 cell line after treatment with (C) venetoclax and (D) S63845. Mean±SD, n=3.

(E) IP of BIM in MOLM-13 cell line to detect binding with MCL-1 and BCL-2 following 1h treatment with venetoclax and S63845

(F) Cell viability heatmap of indicated AML cell lines at 24 h treatment with venetoclax and S63845 (n= 3).

(G) Spearman correlation between Loewe synergy score for venetoclax and S63845 combination and delta priming response to BAD+MS-1 peptides shown in A and B.

(H) % hCD45+ leukemic cells in AML PDX subjected to venetoclax (50 mg/kg, PO, 5 days/week), S63845 (25 mg/kg, IV, 2 days/week) or combination. Mean±SEM, n=5 mice;

*P<0.05, **P<0.01, one-way ANOVA.

See also Figure S4.