Over‐Expression of Cancer Testis Antigen Genes in Multiple Myeloma Stem Cell‐like Cells

Abstract

Multiple myeloma (MM) stem cells, proposed to be responsible for the tumorigenesis, drug resistance and recurrence are enriched in the side population (SP) cells. Cancer testis antigens (CTAs) are attractive targets for immunotherapy since they are widely expressed in cancers but only in limited types of normal tissues. We designed the high throughput real‐time PCR assay allowing simultaneously relative quantifying expression of 90 CTA genes associated with MM. We firstly analyzed the CTA genes expression profile in SP cells of MM cell lines: RPMI8226, MM1S, and U266. In comparison with mature plasma cells (MPCs), 16, 13, and 11 CTA genes were up‐regulated in SP of abovementioned 3 cell lines respectively. 6 CTA genes have overlap in 2 of 3 cell lines, and genes LUZP4 and ODF1 are universally up‐regulated in all 3 MM cell lines. Subsequently, primary bone marrow (BM) from 8 MM patients and 4 healthy donors were studied, and we found that 19 CTA genes were up‐regulated in SP cells of MM BM compared with their MPCs. Notably, expression level of 6 CTA genes were increased in SP cells of both MM BM and at least 1 MM cell line. In contrast, only 2 CTA genes had moderate increase in SP cells of healthy BM compared with their MPCs. Our findings indicates that multiple CTAs are highly expressed in SP cells of both MM cell lines and patient's BM, suggesting potential molecular targets for immunotherapy and other targeted therapy specific for MM.