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. 2018 Jul 15;33(1):262–266. doi: 10.1038/s41375-018-0201-2

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© The Author(s) 2018

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. 2 — S63845 strongly synergizes with venetoclax in killing T-ALL cells in vivo. a Representative zebrafish embryos transplanted with T-ALL cells isolated from Tg(rag2:Myc; rag2:EGFP) zebrafish and treated with vehicle, S63845 (10 μM), venetoclax (10 μM), and the combination of S63845 and venetoclax (10 μM of each). b Quantification of GFP-positive leukemic area in zebrafish embryos and compared with vehicle treatment with the two-tailed Welch’s t test: *P < 0.05; ***P < 0.001. c Synergistic effects of S63845 and venetoclax on T-ALL cell kill were analyzed by isobologram analysis. A combination index (CI) of 1 indicates an additive effect, CI < 1 a synergistic effect and CI > 1 indicates antagonism. d The combination treatment of S63845 and venetoclax significantly extended the overall survival of T-ALL bearing embryos. Zebrafish embryos transplanted with T-ALL cells were treated as indicated for 4 days, with drug refreshment every 2 days, and then the drugs were removed before feeding was initiated and the developing zebrafish larva were observed for 10 more days (n = 12 for CTR, S63845, and venetoclax treatment groups; n = 13 for combined treatment group)