Although studies in nonmyeloma or myeloma cell lines have suggested that acquired resistance enhanced proteasome activity and/or promoted mutations in the CT-L-related β5 proteasomal subunit that impaired BTZ binding [19, 37]; mutations have not been detected in the PSMB5 gene of multiple myeloma (MM) patients being refractory to or relapsed from BTZ treatment [24, 25]. This evidence concerns the gene CASC3 and plasma cell myeloma.