The expression of multiple cancer/testis antigens can potentially be used to detect circulating disease and clonal evolution in the peripheral blood of multiple myeloma patients
Karen Shires1, Teagan Van Wyk2, Kirsty Wienand3
1Division of Haematology, Department of Pathology, University of Cape Town and National Health Laboratory Service/Groote Schuur Hospital, 2Department of Medicine, University of Cape Town, South Africa, 3Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Correspondence to: Karen Shires, Ph.D.
Division of Haematology, UCT Medical School, Anzio Road, Observatory 7221, Cape Town, South Africa
E-mail: Karen.shires@uct.ac.za
Published online: August 30, 2021.
© The Korean Journal of Hematology. All rights reserved.

Abstract
Background: It is thought that cancer/testis antigens (CTAs) are expressed in a cascade-like manner in multiple myeloma as the disease progresses. In this pilot study, we investigated the co-expression of several CTAs in the peripheral blood (PB) during patient therapy to establish whether monitoring multiple CTAs allows for the prediction of relapse and clonal evolution.
Methods: We examined the co-expression of MAGEC1, MAGEA3, PRAME, and BAGE2 via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) duplex assays in the PB mononuclear cells of 10 patients on chemotherapy at 3-month intervals, and correlated the levels to those of two basic clinical monitoring markers, serum β-2-microglobulin and serum M protein. Clonal evolution was investigated using flow cytometry to label the circulating malignant stem cell components with MAGEC1, PRAME, and MAGEA3 antibodies.
Results: Simultaneous monitoring of MAGEC1/PRAME provided sensitive detection of circulating malignant cells in easily accessible PB samples; transcript levels increased prior to changes in indicators of clinical relapse. While MAGEA3/BAGE2 expression levels did not offer earlier prediction of relapse, they provided insight into significant changes occurring within the malignant cell population; the addition of either CTA to a MAGEC1-monitoring panel allowed for better classification of the relapse event (clonal evolution), which in turn could potentially guide treatment strategies in the future.
Conclusion: This pilot study supports the novel idea of determining the levels and CTA expression patterns of the total circulating malignant cell population (pro-B/pre-B stem cell progenitors and proliferating plasma cells) as an alternate disease monitoring methodology.
Keywords: CTA, MAGEC1, Myeloma, Cascade, Monitoring, PRAME


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