Heterogeneous activities of inhibitors of antiapoptotic molecules in BCP-ALL PDX samples. (A) BCP-ALL PDX samples were cultured for 24 hours and exposed to 11 increasing concentrations (0.1, 1, 2.5, 5, 10, 25, 50, 100, 500, 1000, and 5000 nM) of the BCL-2/BCL-XL inhibitor AZD4320. Relative cell death rates were assessed by propidium iodide (PI) staining and normalized to dimethyl sulfoxide controls. EC₅₀ values were calculated, showing a range from 0.47 to 100.30 nM and a median EC₅₀ value of 7.60 nM. (B) Comparison of the sensitivities of inhibitors of BCL-2 and BCL-XL (AZD4320), BCL-2 (venetoclax), or BCL-XL (A-1331852). The scatterplot shows EC₅₀ values of the inhibitors, with each data point representing the EC₅₀ value of 1 PDX sample. The medians are shown as solid lines. Mann-Whitney U test; P values represent significance. (C) Association of venetoclax and AZD4320 sensitivities. (D) Association of A-1331852 and AZD4320 sensitivities. (E) BCP-ALL PDX samples were cultured for 24 hours and exposed to 11 increasing concentrations (0.1, 1, 2.5, 5, 10, 25, 50, 100, 500, 1000 and 5000 nM) of the MCL-1 inhibitor AZD5991. Relative cell death rates (PI) were assessed, and EC₅₀ values were calculated, resulting in a range from 13.93 nM to 51.86 μM and a median of 267 nM. (F) Comparison of the EC₅₀ values of both MCL-1 inhibitors. Mann-Whitney U test; P values, significance. (G) Association of S63845 and AZD5991 sensitivities. (H) Association of the sensitivities of the MCL-1 inhibitor AZD5991 and the BCL-2/BCL-XL inhibitor AZD4320. EC₅₀ values of venetoclax, A-1331852, and S63845 have been published previously.⁷ Spearman correlation; r represents correlation coefficient; P value, significance.