Ex vivo drug screening identifies synergies between dasatinib and AKT inhibitor in killing dexamethasone-resistant zebrafish T-ALL. (A) Schematic of experimental design. (B) Comparison of single and combination drug responses in primary (triangles) and transplanted ALL (circles). T-ALL samples are denoted by filled shapes, whereas B-ALL samples are represented as open shapes. Samples with the same color originate from the same primary leukemia (orange, blue, and green). (C) Representative dose-response curves for sensitive (red line) and insensitive ALLs (blue line) to single drug treatment with dexamethasone (Dex), MK-2206, or dasatinib (Das). (D) Dose-response curves following single drug and combination therapy for a representative, transplanted lck:cMyc T-ALL (L1.5). Green line highlights synergistic drug combinations. (E) Isobolograms normalized to the IC50 of each drug. Combination index average (CI_average) derived from all experimental data points with <1 indicating synergy. Error bars ± standard error of the mean (SEM). n = 3 samples/data point (C-E). ∗P < .05; ∗∗P < .01 by Student 2-tailed t test.