Abstract 1543: Up-regulation of CD52 enhances the resistance against bortezomib in multiple myeloma cells

Abstract

Abstract Bortezomib has excellent clinical activity in patients with multiple myeloma (MM). Clinical efficacy has been hampered by the emergence of drug-resistance phenomena. Verification of molecular mechanism by which resistance emerges is crucial for improved treatment outcome in MM. In this study, we established bortezomib resistance MM cells (U266/velR) and examined the biologic characteristics. In microarray analysis, 294 genes expressions were changed more than two-fold or greater and seven putative genes were selected by further analyzing microarray dataset. Those gene expressions between U266/velR and its control were confirmed using real-time RT-PCR. Among them, CD52, the lymphocyte surface marker, could be a target molecule to overcome bortezomib resistance. CD52 gene expression was examined in 6 different MM cell lines. Its expression was detected in U266, ARH77, and HS-sultan, but not in RPMI8226, IM9 and 536MM. The expression level of CD52 was correlated to the response of Bortezomib sensitivity. FASC analysis showed that CD52+ populations in U266/velR were 2.7 fold higher than those in control. When U266 cells were serially treated with Bortezomib, CD52 expression was gradually increased. In transfection analysis using full length cDNA of CD52 gene, transfected RPMI8226 cells were more resistant than parental cell. Our results suggested that Alemtuzumab was proposed as a therapeutic agent in bortezomib resistant myeloma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1543.