The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

Abstract

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN and XBP1). mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.

Prognostic Value of Resistance Proteins in Plasma Cells From Multiple Myeloma Patients Treated With Bortezomib

“…There are also reports demonstrating that some cell lines resistant to bortezomib have increased expression of POMP [12,29]. It has been previously documented that serum POMP mRNA was significantly up-regulated in MM patients refractory to bortezomib-based treatment [30]. However, in the present study, bortezomib sensitive and refractory patients demonstrated similar levels of POMP expression in MM at the protein level, probably due to the relatively low number of patients.…”