ALCLs depend in their survival on MYC signaling. (A) Western blot analysis of MYC expression in 6 ALCL cell lines and in the MM cell line U266. All ALCL cell lines have detectable MYC expression compared with the negative control U266. (B) Immunohistochemical MYC staining of an MYC-positive ALCL case (left) and an MYC-negative ALCL case (right) (original magnification ×320). (C) MYC shRNA #1 and #2 significantly downregulate MYC protein 96 hours after induction measured by western blotting in K299, DEL, FE-PD, and Mac-2A cells. (D) shRNA-mediated MYC knockdown is toxic to ALCL cell lines. Baseline expression of MYC in the investigated cell lines based on western blotting (seen in panel A) and the ALK translocation status are indicated. Representative results are shown. (E) Expression of an MYC cDNA rescues DEL, JB6, and FE-PD cells, transduced with MYC shRNA #2 (targeting the 3′UTR [untranslated region] of MYC) from toxicity. Representative results from 2 independent replicates are shown. (F) Expression of an MYC cDNA rescues DEL cells, transduced with IRF4 shRNA #1 and #2 from toxicity. In contrast, JB6 and FE-PD cells are not rescued from shRNA-induced toxicity. Representative results from at least 2 independent replicates are shown. (G) ALCL cell lines are sensitive to MYC inhibition using the BET family inhibitor JQ1 after 3 days of incubation. Viability of the negative control cell line U266 is not affected by JQ1. Baseline expression of MYC in the investigated cell lines based on western blotting (seen in panel A) is indicated. Representative results of 3 replicates are shown.