Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma.
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Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma. / Atanackovic, Djordje; Luetkens, Tim; Hildebrandt, York; Arfsten, Julia; Bartels, Katrin; Horn, Christiane; Stahl, Tanja; Cao, Yanran; Zander, Axel R.; Bokemeyer, Carsten; Kröger, Nicolaus.
In: CLIN CANCER RES, Vol. 15, No. 4, 4, 2009, p. 1343-1352.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Longitudinal analysis and prognostic effect of cancer-testis antigen expression in multiple myeloma.
AU - Atanackovic, Djordje
AU - Luetkens, Tim
AU - Hildebrandt, York
AU - Arfsten, Julia
AU - Bartels, Katrin
AU - Horn, Christiane
AU - Stahl, Tanja
AU - Cao, Yanran
AU - Zander, Axel R.
AU - Bokemeyer, Carsten
AU - Kröger, Nicolaus
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 15
SP - 1343
EP - 1352
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 4
M1 - 4
ER -
