Published online 16 December 2009
Haematologica, Vol 95, Issue 5, 785-793 doi:10.3324/haematol.2009.014464
Copyright © 2010 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Atanackovic et al. Supplementary Appendix
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (1)
Google Scholar
Right arrow Articles by Atanackovic, D.
Right arrow Articles by Kröger, N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Atanackovic, D.
Right arrow Articles by Kröger, N.
Related Collections
Right arrowRelated Article

Multiple Myeloma

Cancer-testis antigens MAGE-C1/CT7 and MAGE-A3 promote the survival of multiple myeloma cells

Djordje Atanackovic1, York Hildebrandt2, Adam Jadczak2, Yanran Cao1, Tim Luetkens1, Sabrina Meyer1, Sebastian Kobold1, Katrin Bartels1, Caroline Pabst1, Nesrine Lajmi1, Maja Gordic1, Tanja Stahl1, Axel R. Zander2, Carsten Bokemeyer1, Nicolaus Kröger2

1 Departments of Oncology/Hematology Hubertus Wald Tumorzentrum and
2 Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Correspondence: Djordje Atanackovic, M.D. Department of Medicine II, Oncology/Hematology, University Medical Center, Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. E-mail: D.Atanackovic{at}uke.uni-hamburg.de

Background: Multiple myeloma is a life-threatening disease and despite the introduction of stem cell transplantation and novel agents such as thalidomide, lenalidomide, and bortezomib most patients will relapse and develop chemoresistant disease. Therefore, alternative therapeutic modes for myeloma are needed and cancer-testis antigens such as MAGE-C1/CT7 and MAGE-A3 have been suggested to represent a class of tumor-specific proteins particularly suited for targeted immunotherapies. Surprisingly, the biological role of cancer-testis genes in myeloma remains poorly understood.

Design and Methods: We performed the first investigation of the function of two cancer-testis antigens most commonly expressed in myeloma, MAGE-C1/CT7 and MAGE-A3, using an RNA interference-based gene silencing model in myeloma cell lines. Functional assays were used to determine changes in proliferation, cell adhesion, chemosensitivity, colony formation, and apoptosis resulting from gene-specific silencing.

Results: We show that the investigated genes are not involved in regulating cell proliferation or adhesion; however, they play an important role in promoting the survival of myeloma cells. Accordingly, knock-down of MAGE-C1/CT7 and MAGE-A3 led to the induction of apoptosis in the malignant plasma cells and, importantly, both genes were also essential for the survival of clonogenic myeloma precursors. Finally, silencing of cancer-testis genes further improved the response of myeloma cells to conventional therapies.

Conclusions: Cancer-testis antigens such as MAGE-C1/CT7 and MAGE-A3 play an important role in promoting the survival of myeloma cells and clonogenic precursors by reducing the rate of spontaneous and chemotherapy-induced apoptosis and might, therefore, represent attractive targets for novel myeloma-specific therapies.

Key words: cancer-testis antigens, gene function, RNAi, apoptosis, tumor immunology, multiple myeloma, stem cell transplantation.


Related Article

Novel drugs for the treatment of multiple myeloma
Joan Bladé, Ma Teresa Cibeira, Laura Rosiñol
Haematologica 2010 95: 702-704. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 haematolHome page
J. Blade, M. T. Cibeira, and L. Rosinol
Novel drugs for the treatment of multiple myeloma
Haematologica, May 1, 2010; 95(5): 702 - 704.
[Full Text] [PDF]