Activation of MALT1 is caused by constitutive BCR signaling in MCL. (A) Western blot analysis of CD79A, CARD11, CYLD, RelB, and BCL10 following shRNA-mediated knockdown of CD79A and CARD11, respectively. Cleavage of CYLD, RelB, and BCL10 was significantly downregulated following CD79A or CARD11 knockdown, respectively, in MALT1-activated cell lines (Jeko-1 and Rec-1), whereas none of these cleaved forms was detectable in MALT1-inactive cell lines (Maver-1 and Z-138) and the expression levels of the corresponding full-length forms were not affected. (B) shRNA-mediated knockdown of CD79A and CARD11 was toxic to the MALT1-activated cell lines Jeko-1 and Rec-1. In contrast, the MALT1-inactive cell lines Maver-1 and Z-138 were unaffected by CD79A and CARD11 knockdown. A previously described, nontoxic shRNA against MSMO1 did not induce toxicity in any cell line. Data are shown as means ± standard deviations (SDs) of at least 3 independent experiments. (C) Cell viability of MCL cell lines after incubation with the BTK inhibitor ibrutinib. Representative results from at least 3 independent replicates are shown. Error bars indicate SDs.