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High throughput quantitative reverse transcription PCR assays revealing over‐expression of cancer testis antigen genes in multiple myeloma stem cell‐like side population cells
Author(s) -
Wen Jianguo,
Li Hangwen,
Tao Wenjing,
Savoldo Barbara,
Foglesong Jessica A.,
King Lauren C.,
Zu Youli,
Chang ChungChe
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12951
Subject(s) - side population , cancer research , biology , multiple myeloma , stem cell , population , antigen , immunotherapy , cancer stem cell , gene knockdown , cell , microbiology and biotechnology , cell culture , cancer , immunology , medicine , genetics , environmental health
Summary Multiple myeloma ( MM ) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell‐like side population ( SP ). Cancer testis antigens ( CTA ) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM . In the three MM cell lines tested, six CTA genes were over‐expressed in two and LUZP 4 and ODF 1 were universally up‐regulated in all three cell lines. Subsequent study of primary bone marrow ( BM ) from eight MM patients and four healthy donors revealed that 19 CTA genes were up‐regulated in SP of MM compared with mature plasma cells. In contrast, only two CTA genes showed a moderate increase in SP cells of healthy BM . Furthermore, knockdown using small interfering RNA (si RNA ) revealed that LUZP 4 expression is required for colony‐forming ability and drug resistance in MM cells. Our findings indicate that multiple CTA have unique expression profiles in MM SP , suggesting that CTA may serve as targets for immunotherapy that it specific for MM stem cells and which may lead to the long‐term cure of MM .