Efficacy of BCL-XL inhibition in a xenograft mouse model and in long-term combination treatments. (A) Schematic of the mouse xenograft experiment performed using HEL erythroleukemia cells. (B) Line graph showing tumor burden based on bioluminescence imaging for each mouse relative to start of treatment (day 0). Dashed line indicates stopping of the drug treatment. (C) Comparison of changes in tumor burden between BCL-XL inhibitor and vehicle treatment on day 4 of treatment relative to the start of treatment (day 0) based on bioluminescence imaging. P value was obtained using one-sided Wilcoxon rank-sum test. (D) Schematic of the drug combination screens and bar plot showing the synergy and efficacy score values of the combinations indicating combined efficacy and synergy in all cell lines ranked from highest to lowest on average. (E) Heatmaps of drug sensitivity in HEL erythroleukemia cells with the combinations of A-1331852 with ruxolitinib, venetoclax, and azacitidine across the tested concentration matrices. Percent inhibition values are indicated in the heatmaps. (F) Long-term drug treatment assays using TF1 (erythroid AML), CMK (megakaryocytic AML), and HEL-Luc (erythroid AML, used in mouse studies) cells. Gray-row shaded areas indicate duration of drug treatment.