PURPOSE: Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets. EXPERIMENTAL DESIGN: Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2). RESULTS: CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myeloma patients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-C1, represents an important indicator of early relapse and dramatically reduced survival. CONCLUSIONS: Our findings suggest that CT antigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a "gatekeeper" gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CT antigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.
PURPOSE: Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets. EXPERIMENTAL DESIGN: Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2). RESULTS: CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myelomapatients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myelomapatients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-C1, represents an important indicator of early relapse and dramatically reduced survival. CONCLUSIONS: Our findings suggest that CT antigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a "gatekeeper" gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CT antigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.
Authors: Mark van Duin; Annemiek Broyl; Yvonne de Knegt; Hartmut Goldschmidt; Paul G Richardson; Wim C J Hop; Bronno van der Holt; Debora Joseph-Pietras; George Mulligan; Rachel Neuwirth; Surinder S Sahota; Pieter Sonneveld Journal: Haematologica Date: 2011-07-26 Impact factor: 9.941
Authors: Aaron P Rapoport; Nicole A Aqui; Edward A Stadtmauer; Dan T Vogl; Yin Yan Xu; Michael Kalos; Ling Cai; Hong-Bin Fang; Brendan M Weiss; Ashraf Badros; Saul Yanovich; Gorgun Akpek; Patricia Tsao; Alan Cross; Dean Mann; Sunita Philip; Naseem Kerr; Andrea Brennan; Zhaohui Zheng; Kathleen Ruehle; Todd Milliron; Scott E Strome; Andres M Salazar; Bruce L Levine; Carl H June Journal: Clin Cancer Res Date: 2014-02-11 Impact factor: 12.531
Authors: Djordje Atanackovic; York Hildebrandt; Adam Jadczak; Yanran Cao; Tim Luetkens; Sabrina Meyer; Sebastian Kobold; Katrin Bartels; Caroline Pabst; Nesrine Lajmi; Maja Gordic; Tanja Stahl; Axel R Zander; Carsten Bokemeyer; Nicolaus Kröger Journal: Haematologica Date: 2009-12-16 Impact factor: 9.941
Authors: Otavia L Caballero; Qi Zhao; Donata Rimoldi; Brian J Stevenson; Suzanne Svobodová; Sylvie Devalle; Ute F Röhrig; Anna Pagotto; Olivier Michielin; Daniel Speiser; Jedd D Wolchok; Cailian Liu; Tanja Pejovic; Kunle Odunsi; Francis Brasseur; Benoit J Van den Eynde; Lloyd J Old; Xin Lu; Jonathan Cebon; Robert L Strausberg; Andrew J Simpson Journal: PLoS One Date: 2010-09-16 Impact factor: 3.240