Fig. 5: PRMT5 inhibition or depletion attenuates MCL tumor growth in both CDX and PDX models.

NSG mice xenografts implanted with a Granta-519 or d Maver-1 were treated with either vehicle solvent or PRMT5 inhibitor GSK3326595 (100 mg/kg, daily). Tumor volumes were measured and plotted against the time of treatment (n = 5). Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by a two-way ANOVA test. Tumor weights of b Granta-519 and e Maver-1 xenografts from (a) and (d), respectively, were measured at the endpoint of treatment. Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by a two-tailed independent Student’s t test. c, f Western blotting analysis of the expression of PRMT5, H4R3me2s, p53, and p21 in xenograft tumors from (a) and (d), respectively. g Granta-519 cells with or without PRMT5 KO were injected into NSG mice. Tumor volume was monitored and plotted. Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by two-way ANOVA test. h Tumor weights at the endpoint are presented. Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by two-tailed independent Student’s t test. i PRMT5 expression in tumors of mice was confirmed using western blotting. j PDX models were derived from a MCL patient who had TP53 mutations. The PDX mice were treated with vehicle or GSK3326595 (100 mg/kg, daily). Tumor sizes were measured at different days and plotted relative to the number of days post treatment (n = 5). Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by a two-way ANOVA test. k, l Tumor weight measurement, statistical analysis, and western blotting were performed as described in (b) and (c). m PDX models derived from a MCL patient who had relapsed after CD19 CAR T-cell therapy were treated with GSK3326595 (100 mg/kg, daily). Tumor sizes were measured at different days and plotted against the time of treatment (n = 5). Statistical significance between vehicle and PRMT5 inhibitor treatment was determined by two-way ANOVA test. n, o Tumor weight measurement, statistical analysis, and western blotting were performed as described in (b) and (c). For all panels: *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns (not statistically significant), P ≥ 0.05.