MCLs depend on MYC signaling. (A) shRNA-mediated MYC knockdown induced cytotoxicity in MCL cell lines. A previously described nontoxic shRNA against MSMO1 did not induce toxicity in any cell line. Data are shown as means ± SDs of at least 3 independent experiments. (B) Expression of a MYC cDNA rescued Jeko-1, Rec-1, and SP53 cells transduced with MYC shRNA #2 (targeting the 3′UTR of MYC) from toxicity. Data are shown as means ± SDs of at least 2 independent experiments. (C) Expression of a MYC cDNA partially rescued Jeko-1, Rec-1, and SP53 cells transduced with MALT1 shRNA #1 from toxicity. Data are shown as means ± SDs of at least 2 independent experiments. (D) Expression of an MYC cDNA partially rescued Jeko-1, Rec-1, SP53, and Mino cells treated with z-VRPR-fmk from toxicity. Data are shown as means ± SDs of at least 2 independent experiments. (E) shRNA-mediated knockdown of MYC significantly downregulated cell proliferation. Data are shown as means ± SDs of at least 2 independent experiments. (F) Correlation of Ki-67 and MYC expression determined by immunohistochemistry. Error bars indicate the standard error of the mean. (G) Viability of MCL cell lines following MYC inhibition using the small molecule inhibitor 10058-F4 that inhibits MYC-MAX heterodimerization. Baseline MYC expression was assessed by western blotting (Figure 6A). Representative results from at least 3 independent replicates are shown. Error bars indicate SDs. **P < .01, ***P < .001.