Diff erent expression of genes involved in unfolded protein response in multiple myeloma and extramedullary dis ease patients

Czech version

Authors: A. Dostálová ¹; M. Vlachová ¹; T. Růžičková ¹; P. Vaňhara ^2,3; M. Štork ⁴; S. Ševčíková ^1,5
Authors‘ workplace: Babákova myelomová skupina, Ústav patologické fyziologie, LF MU Brno ¹; Ústav histologie a embryologie, LF MU Brno 4 ²; Výzkumné centrum aplikované molekulární onkologie (RECAMO), MOÚ Brno Interní hematologická a onkologická klinika LF MU a FN Brno ³; Oddělení klinické hematologie, FN Brno ⁵
Published in: Klin Onkol 2025; 38(1): 45-51
Category: Original Articles
doi: https://doi.org/10.48095/ccko202545

Overview

Background: The unfolded protein response (UPR) enables myeloma cells to overcome the stress conditions arising from excessive proteosynthesis and thus provides a survival advantage for myeloma cells. Extramedullary disease is a more aggressive form of multiple myeloma in which myeloma cells lose their dependence on the bone marrow microenvironment and are able to infiltrate other tissues and organs. The pathogenesis of extramedullary disease is not fully elucidated yet. The aim of this study was to determine whether there is a difference in the expression of UPR-related genes between bone marrow plasma cells from multiple myeloma and extramedullary disease patients. Materials and methods: Gene expression of six genes involved in UPR (ERN1, DDIT3, EIF2AK3, TUSC3, XBP1, HSPA5) was analyzed by quantitative reverse transcription polymerase chain reaction. In total, 76 bone marrow plasma cell samples were used, of which 44 were from patients with multiple myeloma and 32 from patients with extramedullary disease. Results: A statistically significant difference was observed between the multiple myeloma and extramedullary disease groups regarding the expression of HSPA5, DDIT3, EIF2AK3, and ERN1 genes. However, in the case of XBP1 and TUSC3 genes, no statistically significant difference in the expression was found. Several statistically significant correlations between the expression levels of the analyzed genes and the clinical data of the patients were observed as well. Conclusion: Our results suggest the importance of UPR in the pathogenesis of extramedullary disease. UPR appears to be a promising avenue for further research.

Keywords:

Multiple myeloma – Plasma cells – unfolded protein response – extramedullary disease

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