Importantly, mutation in BIRC3 is associated with activation of non-canonical NF-κB signaling in MCL and CLL, which is quite different from classical NF-κB activation mediated through BCR signaling, and, therefore, this activation of non-canonical NF-κB signaling instructed resistance to ibrutinib [38,39]. The gene discussed is BIRC3; the disease is mantle cell lymphoma.