BCR and mantle cell lymphoma: For BCR pathway, BTK is indispensable since it worked as a membrane proximal signal molecule for the activation and proliferation of B cell.163 Presently, ibrutinib has been approved for treating MCL and activated B-cell-like (ABC)-DLBCL by covalent binding.164 However, MCL patients have developed drug resistance after receiving ibrutinib treatment due to the missense BTK mutation of C481S.165 Ibrutinib also lost the inhibitory efficacy of DLBCL tumor cell growth resulting from the BTK C481S mutant.