Targeting ROR1 expression augments drug responses for BCR and Bcl-2 inhibitors. (A) DSS values for shRNA Ctr-transduced cells were correlated with the corresponding DSS values for shRNA ROR1-transduced cells to depict differential drug sensitivities and resistance patterns. ● indicates Bcl-2–targeted drugs navitoclax and venetoclax as well as BTK inhibitor ibrutinib for each cell line. (B) Heatmap of DSS values for different apoptotic modulators tested in Jeko-1 and Z-138 shRNA-expressing cells by unsupervised clustering based on average DSS values for each row. (C) Heatmap of DSS values for selective BCR inhibitors functionally relevant in shRNA-expressing Jeko-1 cells. (D) Percentage of cell viability (compared with controls) of untreated or treated cells with ROR1 2A2 mAb (5 µg/mL) for 24 hours followed by addition of indicated drugs for 24 hours. Error bars represent mean plus or minus SD of triplicates. (E) ROR1 silencing enhances venetoclax cytotoxicity in MCL#2 primary cells. Cell viability was measured by PI staining after 24 hours and normalized to the untreated siRNA Ctr sample. (F) Percentage of primary cell viability (compared with controls) of untreated or treated cells with ROR1 2A2 mAb (5 µg/mL) for 24 hours followed by addition of venetoclax for 24 hours. Error bars represent mean plus or minus SD of triplicates. (G) Percentage of viable cells (compared with untreated control) of primary MCL#5 cells cultured alone or in coculture with L-CD40L fibroblasts and the cytokines cocktail and treated with ROR1 2A2 mAb or venetoclax, alone or in combination as indicated. Error bars represent mean plus or minus SD of triplicates. Statistical significances: *P < .05, **P < .01, ***P < .001, calculated by a 2-tailed paired Student t test. ATP, adenosine triphosphate; Conc., concentration; EGFR, epidermal growth factor receptor; FAK, focal adhesion kinase; mTOR, mammalian target of rapamycin; Nav, navitoclax; TKI, tyrosine kinase inhibitor; Ven, venetoclax.