Fig. 6: Inhibition of both MEN1 and EZH2 in EZH2-mutated DLBCL.

a Venn diagram showing the overlaps of up-regulated (left) and down-regulated genes (right) between individual treatments of VTP50469 (330 nM, purple), EPZ-6438 (1 µM, green), and combo treatment of both inhibitors (gray) in KARPAS422 (K422) cells for 48 h. b Venn diagrams showing the overlaps of up-regulated (left) and down-regulated genes (right) between individual treatments of VTP50469 (330 nM, purple), EPZ-6438 (1 µM, green), and combo treatment of both inhibitors (gray) in SuDHL10 (DHL10) cells for 24 h. c Relative percentage of viable Farage or KARPAS422 cells following individual treatments of VTP50469 (160 nM, red), EPZ-6438 (200 nM, yellow), or combo treatment of both inhibitors (purple) for 8 days, normalized to the DMSO-treated controls. n = 3 independent experiments. Bar plots and whiskers are mean ± s.d. For statistical analyses of the relative percentage of viable cells in KARPAS422, p (EPZ-6438 vs. EPZ-6438 + VTP50469) = 0.00203; p (VTP50469 vs. EPZ-6438 + VTP50469) = 0.0115. d Relative percentage of viable EPZ-6438-resistant DB-r cells treated with either EPZ-6438 (1 μM, yellow) or MI-503 (800 nM, red), or both inhibitors for 7 days. n = 4 independent experiments. Bar plots and whiskers are mean ± s.d. For statistical analyses of the relative percentage of viable cells, p (EPZ-6438 vs. EPZ-6438 + MI-503) = 0.00138; p (MI-503 vs. EPZ-6438 + MI-503) = 0.00522. e Volumes of SuDHL10 tumors treated with vehicle, VTP50469 (20 mg/kg), EPZ-6438 (125 mg/kg), or both inhibitors. n = 10 biologically independent animals per group. Dots and whiskers are mean ± SEM. For statistical analyses of tumor volume on Day 28, p (EPZ-6438 vs. vehicle) = 1.31e−5; p (EPZ-6438 + VTP50469 vs. vehicle) = 9.96e−11. f Kaplan–Meier survival curves of mice in each group as indicated in (e). P-values were determined by Log-rank (Mantel–Cox) test between each group and vehicle group. n = 10 biologically independent animals per group. For statistical analyses of the EPZ-6438 treated group and EPZ-6438 + VTP50469 treated group, p < 0.0001 for both groups when each compared to the vehicle group. For all experiments, p values were determined by unpaired two-tailed Student’s t-test. *p < 0.05; **p < 0.01; ***p < 0.001. Source data are provided as a Source Data file.