Development of MCL cell line models of PRMT5 inhibitor resistance and shared protein expression signatures across resistant models. (A) Increased IC50s for PRT-382 and PRT-808 of PRMT5 inhibitor resistance resistant (red) vs original sensitive (blue) MCL cell lines in SP53, Z-138, REC-1, and CCMCL. (B) Resistant PDX and cell lines of MCL achieve similar reduction in SDMA at their original and resistant day 9 IC₅₀s and no substantial change in ADMA or PRMT5 after 6 days of drug exposure. Protein levels were normalized to the sensitive untreated condition in each model. ∗ P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.