Fig. 3. Combination therapy exhibits synergy in AML cells.

FACI (combination index as a function of fraction affected) plots for combination treatment with CCCP and 2-DG in OCI-AML2, healthy PBMCs, and SKOV3 cells (a) or primary AML cells for one (upper) or multiple (n = 21, lower) patients (b). Non-linear regression was used to generate a function for combined FACI data for primary AML samples. c Drug combination landscapes for OCI-AML2 cells and normal PBMCs built using the Bioconductor package ‘synergyfinder’¹⁷. d Viability of OCI-AML2 cells and normal PBMCs after treatment with CCCP/2-DG at LD25 concentrations corresponding to OCI-AML2 cell line. e ATP level before and after treatment with CCCP and 2-DG in AML cell lines, healthy PBMCs, and solid tumor cell lines (upper) or primary AML samples (lower). f Respiration (upper) and coupling efficiency (lower) before and after treatment with CCCP, 2-DG, or both. g Viability of OCI-AML2 and normal PBMC cells after treatment with ABT-199/2-DG. All graphs show results from at least three independent experiments (except b, where primary AML cells were limited by patient samples). FACI plots reflecting combination indices with 95%-confidence intervals were built using the Bioconductor package ‘drc’¹⁶, * significant difference from combination index = 1 (additivity). Elsewhere, results are presented as mean ± SD (d, e, g) or mean ± SEM (f). Statistical significance was tested using Student’s t-test with independent samples (d, e, g) or by ANOVA with subsequent Dunn’s test (f). ***p < 0.001; **p < 0.01; *p < 0.05; ns: p > 0.05