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)