PRMT5 inhibition is therapeutic in xenograft models derived from patients with MCL. (A-C) PDX-DA. (A) Experimental design of PDX-DA. Treatment with VC (n = 5), ibrutinib (0.16 mg/mL in drinking water; n = 5), or PRT-382 (10 mg/kg 4D3D; n = 5) was started 26 days after engraftment. In the crossover treatment group (n = 7), PRT-382 was added at day 33 and ibrutinib was discontinued on day 45. (B) Circulating disease in peripheral blood of mice was quantified by staining for the percentage of human CD19⁺/CD5⁺ cells detected by flow cytometry. (C) Survival was assessed by Kaplan-Meier survival analysis. (D-J) PDX-AA. (D) Experimental design of PDX-AA. Treatment with VC (n = 5), ibrutinib (0.21 mg/mL in drinking water; n = 5), or PRT-382 (10 mg/kg 4D3D; n = 5) was started on day 25 after engraftment. (E) Circulating disease in peripheral blood of mice was quantified by staining for the percentage of human CD19⁺/CD5⁺ cells detected by flow cytometry. (F) Survival was assessed by Kaplan-Meier survival analysis. (G) Average spleen weight in grams after 1 and 2 weeks of treatment and at ERC. (H) Cell proliferation was assessed by staining for Ki67 in spleens of mice treated in vivo for 1 and 2 weeks. (I) Spleens of mice treated in vivo were harvested after 2 weeks of treatment and human CD19⁺ cells were isolated and immunoblotted for H4R3me2s, SDMA, and ADMA. β-Actin was used as a loading control. (J) Protein expression densitometry values normalized to β-actin and relative to VC sample in lane 1. Each dot represents an individual mouse.