van Duin, Mark, Broyl, Annemiek, de Knegt, Yvonne, Goldschmidt, Hartmut, Richardson, Paul G., Hop, Wim C.J., van der Holt, Bronno, Joseph-Pietras, Debora, Mulligan, George, Neuwirth, Rachel, Sahota, Surinder S. and Sonneveld, Pieter
Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy
Haematologica, 96, (11), . (doi:10.3324/haematol.2010.037978). (PMID:21791470).
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Background. In multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens, which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis.
Design and Methods. Evaluation of cancer testis antigen expression was performed in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens, of which 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients and were evaluated in detail.
Results. For 58 out of 87 cancer testis antigens tissue restriction was known. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of the relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival.
Conclusions. Relapse multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed MM patients and in relapse MM patients. The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register nr NTR-213. CREST, SUMMIT and APEX trials were registered under numbers M34100-024, M34100-025 and NCT00049478/ NCT00048230, respectively.
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