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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. 6 — Cell death was assessed upon exposure of BCP-ALL cell lines to increasing concentrations of venetoclax and/or A-1331852 for 48 h. A The heatmaps show dose-response matrix analyses based on cell death assessed by propidium iodide (PI) staining of the cell lines indicated. N = 3 independent experiments in triplicates. B Interaction landscapes of the combination effects are shown. δ-scores were calculated using synergyfinder. The color encodes the δ-score (red synergistic, white additive effect and green antagonistic) and the Bliss synergy scores shown indicate the average score over the dose-response matrix. C Association of the calculated Bliss synergy scores with the delta priming responses to BAD + HRK (reflecting combined dependence on BCL-2 and BCL-XL) in all cell lines. Spearman correlation; r, correlation coefficient; p, significance. D Annexin V and PI staining following exposure to 10 nM venetoclax and/or 100 nM A-1331852 for 48 hours. Quantification of viable cells (Annexin V-/PI-), early apoptotic cells (Annexin V + /PI-), late apoptotic cells (Annexin V + /PI + ) and necrotic cells (Annexin V-/PI + ) is shown. N = 3 independent experiments in triplicates.