Figure 3.
Bulk RNA-seq reveals shared differential gene expression of MCL cell lines and PDX model with PRMT5 inhibitor resistance. Bulk RNA-seq was conducted on the following PDX MCL splenic lymphocyte samples: 3 VC-treated, 3 PRMT5 inhibitor short-term–treated (treated 2 weeks before necropsy), and 2 PRMT5 inhibitor–resistant (treated until ERC) mice and MCL cell lines: dimethyl sulfoxide and PRMT5 inhibitor–treated resistant and sensitive SP53, Z-138, REC-1, and CCMCL in triplicate. (A) Principal component analysis displaying the relationship between pairs of sensitive (S) and resistant (R) MCL models in which network lines highlight the 2 nearest neighbors for each sample. (B) Bar chart depicting the overlap of differential transcript expression in R and S cell lines relative to R and S of the PDX. Fold enrichment of overlapping gene set vs expected overlap and P value (Fisher exact test) are indicated. (C) Ingenuity pathway analysis identification of dysregulated pathways based on DEGs of PRMT5 inhibitor–treated resistant vs short-term–treated PDX (P < 10-5; z score < −0.3 or > 0.3). (D) This list of pathways was used to filter for shared pathways dysregulated based on DEGs of PRMT5 inhibitor–resistant vs sensitive treated MCL cell lines (P < 10-5; z score < −0.3 or > 0.3).