Cancer testis antigen MAGE C1 can be used to monitor levels of circulating malignant stem cells in the peripheral blood of multiple myeloma patients.

Abstract

Monitoring the levels of malignant disease-causing cells in multiple myeloma, as opposed to the clinical symptoms alone, is an important move forward in the management of this disease. While current methods including multiparametric flow cytometry and PCR analysis of the clonal plasma cells can be used in a patient-specific manner, their use is limited and the fundamental malignant progenitor cell is not being monitored. The expression of cancer testis antigen MAGE C1 has been linked to the malignant stem cell in this disease, and thus, we investigated the use of both flow cytometric and qRTPCR approaches to monitor its expression as an alternative monitoring methodology in this pilot study. We compared the levels of MAGE C1 in the peripheral blood to serum M protein and serum beta 2 microglobulin levels at 3-monthly intervals over a 2-year period, for 12 patients on chemotherapy regimens and 4 patients undergoing stem cell transplantation. The analysis indicated that the novel flow cytometric analysis of MAGE C1 expression in the peripheral blood was extremely relevant as a potential minimal residual disease-monitoring tool. Expression of this cancer testis antigen was detectable in all patients throughout treatment, with comparable increases and decreases to serum M protein and/or serum beta 2 microglobulin, but with the advantage of being able to detect disease at a more sensitive level. Furthermore, due to the increased sensitivity, the ability to pre-empt disease relapse before clinical changes were evident, was preliminarily indicated. The qRTPCR approach showed potential as a monitoring tool in the chemotherapy patient cohort, with the mRNA MAGE C1 levels following a similar pattern of expression observed in the flow cytometry analysis.