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. 2022 Jan 14;36(4):901–912. doi: 10.1038/s41375-021-01502-z

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — BCP-ALL cell lines were exposed to increasing concentrations of venetoclax, S63845 or combinations of both inhibitors. A Cell death rates were analyzed by flowcytometry after 48 h by propidium iodide (PI) staining. The heatmaps show cell death rates of dose-response matrix analyses of the cell lines indicated. N = 3 independent experiments in triplicates. B Interaction landscapes of the dose-response matrix analyses are shown. To estimate synergy, δ-scores were calculated using synergyfinder. Synergistic effects are shown in red, additive effects in white and antagonistic effects in green. The shown Bliss synergy score indicates the average synergy score over the dose-response matrix. C Association of the Bliss synergy scores of all cell lines with delta priming response values to BAD + MS1 reflecting combined dependence on BCL-2 and MCL-1. Spearman correlation; r, correlation coefficient; p, significance. D Annexin V and PI staining was assessed upon exposure of cells for 48 h to 10 nM venetoclax and/or 100 nM S63845 to determine apoptotic cells. The fractions of viable cells (Annexin V-/PI-), early apoptotic cells (Annexin V + /PI-), late apoptotic cells (Annexin V + /PI + ) and necrotic cells (Annexin V-/PI + ) are shown. N = 3 independent experiments in triplicates.