Figure 7.

Bioenergetic profiling of immortalized and primary AML cells and healthy PBMCs after treatment with selected drug combinations. (A) Oxygen consumption rate (OCR) was measured using a Seahorse flux analyzer. OCR measured in cells either untreated (blue) or treated with IACS-010759 25 nM/vinorelbine 10 nM (red), rotenone 50 nM/2-deoxy-D-glucose 50 μM (green), CCCP 200 nM/dasatinib 50 nM (purple), or ABT-199 1.3 nM/lonidamine 50 nM (orange) for 2 h. One representative replicate of time-course OCR measurements (mean ± SD) in MOLM-13 cells, representative primary AML sample (AML 13), and healthy PBMCs is shown. See Figure S16 for additional primary cell data. (B) Treatment-induced changes in basal mitochondrial respiration in AML cells (MOLM-13, representative AML sample) or healthy PBMCs. Shown is mean ± SEM. Significance of difference between treated and untreated cells was assessed via ANOVA with subsequent pairwise comparisons. (C) Coupling efficiency of untreated AML cells or healthy PBMCs. Shown is mean ± SEM. Significance of difference vs. PBMCs was assessed via ANOVA with subsequent pairwise comparisons. (D) ATP-linked respiration after IACS/VIN treatment in a panel of AML cells or PBMCs, normalized to DMSO control. Significance of difference vs. PBMCs was assessed via ANOVA with subsequent pairwise comparisons. (E) Significant positive correlation between normalized coupling efficiency, %, and normalized ATP-linked respiration, %, across all studied samples under four selected treatments. (F) Significant negative correlation between normalized levels of ATP, %, and ECAR, %, across all studied samples under four selected treatments. Mito-stress test was repeated three times independently for MOLM-13 cells and PBMCs, and once for each primary AML sample. ^***p < 0.001; ^**p < 0.01; ^*p < 0.05; ns: p > 0.05. Correlations were assessed using Pearson r coefficient, line of best fit represents linear regression line.