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Blood, 15 July 2006, Vol. 108, No. 2, pp. 662-668. Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-12-5125. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: 2005-12-5125v1 108/2/662    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sanchez-Aguilera, A. Articles by Garcia, J. F Search for Related Content PubMed PubMed Citation Articles by Sanchez-Aguilera, A. Articles by Garcia, J. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 27, 2005 Accepted March 1, 2006 Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classical Hodgkin lymphoma Abel Sanchez-Aguilera, Carlos Montalban, Paloma de la Cueva, Lydia Sanchez-Verde, Manuel M Morente, Monica Garcia-Cosio, Jose Garcia-Larana, Carmen Bellas, Mariano Provencio, Vicens Romagosa, Alberto Fernandez de Sevilla, Javier Menarguez, Pilar Sabin, Maria J Mestre, Miguel Mendez, Manuel F Fresno, Concepcion Nicolas, Miguel A Piris, and Juan F Garcia* Lymphoma Group, Spanish National Cancer Centre (CNIO), Madrid, Spain Department of Internal Medicine, Hospital Ramon y Cajal, Madrid, Spain Histology and Immunohistochemistry Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain Tumor Bank Network, Spanish National Cancer Centre (CNIO), Madrid, Spain Department of Pathology, Hospital Ramon y Cajal, Madrid, Spain Department of Hematology, Hospital Ramon y Cajal, Madrid, Spain Department of Pathology, Hospital Puerta de Hierro, Madrid, Spain Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain Department of Pathology, Institut Catala d'Oncologia, Barcelona, Spain Department of Hematology, Institut Catala d'Oncologia, Barcelona, Spain Department of Pathology, Hospital Gregorio Maranon, Madrid, Spain Department of Oncology, Hospital Gregorio Maranon, Madrid, Spain Department of Pathology, Hospital de Mostoles, Madrid, Spain Department of Oncology, Hospital de Mostoles, Madrid, Spain Department of Pathology, Hospital Central de Asturias, Oviedo, Spain Department of Hematology, Hospital Central de Asturias, Oviedo, Spain Department of Pathology, M.D.Anderson International, Madrid, Spain; Lymphoma Group, Spanish National Cancer Centre (CNIO), Madrid, Spain * Corresponding author; email: jfgarcia{at}mdanderson.es. Around 20-30% of Hodgkin Lymphoma (HL) patients do not benefit from standard therapies and finally succumb to their disease. The factors that influence the outcome of HL have not been elucidated, underscoring the demand for the identification of biological risk factors and new therapeutic targets. We analyzed the gene-expression profiles of samples from 29 patients with advanced classical HL treated with standard therapy, and compared the expression profiles of patients with favorable and unfavorable clinical outcome. Using supervised methods, we identified 145 genes associated with outcome, which were grouped into four signatures representing genes expressed by either the tumoral cells (genes involved in the regulation of mitosis and cell growth/apoptosis) or the tumor microenvironment. The relationship between the expression of eight representative genes and survival was successfully validated in an independent series of 235 patients by quantification of protein expression levels on tissue-microarrays. Analysis of centrosomes and mitotic checkpoint confirmed the existence of an abnormal transition through mitosis in HL cells. Therefore, genes related with tumor microenvironment, cell growth/apoptosis, and regulation of mitosis are associated with treatment response and outcome of HL patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. A. Doussis-Anagnostopoulou, T. P. Vassilakopoulos, I. Thymara, P. Korkolopoulou, M. K. Angelopoulou, M. P. Siakantaris, S. I. Kokoris, E. M. Dimitriadou, C. Kalpadakis, M. Matzouranis, et al. Topoisomerase II{alpha} Expression as an Independent Prognostic Factor in Hodgkin's Lymphoma Clin. Cancer Res., March 15, 2008; 14(6): 1759 - 1766. 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Lee, M.-K. Kim, M.-K. Han, H. Shibayama, S. Fukuda, M. C. Yoder, L. M. Pelus, K.-S. Kim, et al. Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability Blood, May 15, 2007; 109(10): 4518 - 4527. [Abstract] [Full Text] [PDF]

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