Fig. 8

Inhibition of IDH2 by AGI-6780 suppressed AML survival in vitro and in vivo. a, b Effect of AGI-6780 on cell proliferation in U937 and ML-1 cells. Cells were treated with AGI-6780 (10 µM) or solvent (DMSO), and cell numbers were counted at the indicated time points. Data are mean ± SD of three experiments. c Levels of protein expression of IDH2 and C-MYC in U937 and ML-1 cells treated with AGI-6780 (10 µM) or solvent (DMSO) for 24 h. d The indicated cell line were treated with AGI-6780 for 72 h, and cell viability was measured using MTS assay. e Primary leukemia cells from AML patients with wt-IDH2 (n = 4) and normal human bone marrow cells (HBMC) were treated ex vivo with the indicated concentrations of AGI-6780 for 72 h, and cell viability was measured using MTS assay. f Comparison of percentage of Annexin V/PI-negative cells in primary AML cells and primary normal bone marrow cells treated with 10–20 µM AGI-6780 for 48 h. The original flow cytometry analysis data are presented as Additional file 3: Fig. S8c, d. g Protein levels of IDH2 and C-MYC in primary AML cells treated with AGI-6780 (20 µM) or with solvent (DMSO) for 24 h. h Growth curves of AML xenografts in athymic nude mice inoculated with ML-1 cells harboring wt-IDH2 (n = 6 per group, mean ± SEM). Mice were treated with daily i.p. injection of AGI-6780 or solvent as indicated. i Photographs of gross tumors isolated from mice at the end of the experiment. j Western blot analysis of C-MYC expression in tumor tissues of ML-1 xenografts isolated from mice treated with AGI-6780 or solvent as indicated. k Tumor weights of each group at the end of the experiment (mean ± SEM). l Relative C-MYC protein levels in tumor tissues of mice treated with solvent (n = 6) or AGI-6780 (n = 6). m Mouse body weights (mean ± SD). Two-tailed unpaired student’s t test for a, b, f, h, k and l, *p < 0.05, ***p < 0.001