Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 9 December 2020 / Approved: 11 December 2020 / Online: 11 December 2020 (15:50:15 CET)
Version 2 : Received: 23 January 2021 / Approved: 25 January 2021 / Online: 25 January 2021 (13:17:31 CET)

How to cite: Robak, P.; Jarych, D.; Mikulski, D.; Drozd, I.; Węgłowska, E.; Kotkowska, A.; Misiewicz, M.; Smolewski, P.; Stawiski, K.; Fendler, W.; Szemraj, J.; Robak, T. The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib. Preprints 2020, 2020120287 (doi: 10.20944/preprints202012.0287.v1). Robak, P.; Jarych, D.; Mikulski, D.; Drozd, I.; Węgłowska, E.; Kotkowska, A.; Misiewicz, M.; Smolewski, P.; Stawiski, K.; Fendler, W.; Szemraj, J.; Robak, T. The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib. Preprints 2020, 2020120287 (doi: 10.20944/preprints202012.0287.v1).

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.

Keywords

ABCB1; bortezomib; CXCR4; gene expression; MAF; MARCKS; multiple myeloma; mRNA; POMP; PSMB5; refractory; RPL5; TXN; XBP1; sensitive

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