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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3345-3351. Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-02-075036. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-02-075036v1 110/9/3345    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rodríguez-Antona, C. Articles by Martínez-Delgado, B. Search for Related Content PubMed PubMed Citation Articles by Rodríguez-Antona, C. Articles by Martínez-Delgado, B. Related Collections Neoplasia Gene Expression Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas Cristina Rodríguez-Antona1, Susanna Leskelä1, Magdalena Zajac2, Marta Cuadros2, Javier Alvés3, Maria Victoria Moneo4, Carmen Martín5, Juan Cruz Cigudosa5, Amancio Carnero4, Mercedes Robledo1, Javier Benitez2, and Beatriz Martínez-Delgado2 1 Hereditary Endocrine Cancer Group 2 Human Genetics Group, Spanish National Cancer Centre, Madrid; 3 Department of Pathology, Hospital La Paz, Madrid; 4 Molecular Cytogenetics Group and 5 Assay Development Group, Spanish National Cancer Centre, Madrid, Spain Peripheral T-cell lymphomas (PTCLs) are aggressive tumors in which the current therapy based on multiagent chemotherapy is not successful. Since cytochrome P450 3A subfamily (CYP3A) enzymes are involved in the inactivation of chemotherapy drugs, we hypothesized that CYP3A and P-glycoprotein (MDR1) expression in these lymphomas could result in a poor clinical response. We measured tumoral CYP3A and MDR1 mRNA content in 44 T-cell lymphomas, finding a large variation in CYP3A expression. Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. To test whether the tumoral expression of CYP3A and/or MDR1 could influence PTCL treatment outcome, their expression levels were compared with the clinical response and survival of the patients, finding that a high tumoral expression of CYP3A4 was significantly associated with a lower complete remission rate. This was further investigated with cell lines stably expressing CYP3A4 that exhibited an increased resistance to doxorubicin and etoposide. In conclusion, a high CYP3A4 tumoral expression could be useful to predict poor response to the standard PTCL chemotherapy; in these cases alternative chemotherapy combinations or doses should be explored. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C Agostinelli, P P Piccaluga, P Went, M Rossi, A Gazzola, S Righi, T Sista, C Campidelli, P L Zinzani, B Falini, et al. Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies J. Clin. Pathol., November 1, 2008; 61(11): 1160 - 1167. [Abstract] [Full Text] [PDF]

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