Ibrutinib-resistant MCL cell lines (based on the therapeutic dose of 560 mg = 0.4 μg/μl) possessing a lack of normal BTK expression or presence of mutant BTK (C481S) were characterized by failure to inhibit phosphorylation of ERK and Akt signaling pathways, sustained PI3K-AKT activity, and activation of alternative NFκB pathway [153, 154]. This evidence concerns the gene AKT1 and mantle cell lymphoma.