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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4752-4758. Prepublished online as a Blood First Edition Paper on February 15, 2005; DOI 10.1182/blood-2004-11-4544. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4544v1 105/12/4752    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 Rocha, J. C. C. Articles by Relling, M. V. Search for Related Content PubMed PubMed Citation Articles by Rocha, J. C. C. Articles by Relling, M. V. Related Collections Neoplasia Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Pharmacogenetics of outcome in children with acute lymphoblastic leukemia Jose Claudio C. Rocha, Cheng Cheng, Wei Liu, Shinji Kishi, Soma Das, Edwin H. Cook, John T. Sandlund, Jeffrey Rubnitz, Raul Ribeiro, Dario Campana, Ching-Hon Pui, William E. Evans, and Mary V. Relling From the Hematologic Malignancies Program, Department of Pharmaceutical Sciences, the Department of Hematology-Oncology, and the Department Biostatistics, Saint Jude Children's Research Hospital of the University of Tennessee, Memphis; and the Department of Psychiatry, Pediatrics, and Human Genetics, University of Chicago, Chicago, IL. Acquired genetic characteristics of acute lymphoblastic leukemia (ALL) cells are used to individualize therapy, whereas germ line genetic characteristics generally are not. We determined whether ALL outcome was related to 16 genetic polymorphisms affecting the pharmacodynamics of antileukemic agents. Of 246 children, 116 were treated on the lower-risk (LR) and 130 on the higher-risk (HR) arms of a St Jude protocol. Patients in the HR group with the glutathione S-transferase (GSTM1) nonnull genotype had greater risk of hematologic relapse (P = .03), which was further increased by the thymidylate synthetase (TYMS) 3/3 genotype (P = .03). These genotypes remained predictive in multivariate analyses (P < .001 and .003, respectively). No genotypes were predictive in the LR arm. Expression of these 2 genes in ALL blasts was lower in those with low-activity genotypes. For central nervous system relapse, among the HR group, the vitamin D receptor start site (P = .02) and intron 8 genotypes (P = .04) predisposed, whereas for LR patients the TYMS 3/3 genotype predisposed (P = .04). The GSTM1 non-null and TYMS 3/3 genotypes are plausibly linked to drug resistance. Polymorphisms interact to influence antileukemic outcome and represent determinants of response that can be used to optimize therapy. (Blood. 2005;105:4752-4758) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Toward individualized dosing in pediatric ALL Michel Zwaan Blood 2005 105: 4544-4545. [Full Text] [PDF] This article has been cited by other articles: S. Dulucq, G. St-Onge, V. Gagne, M. Ansari, D. Sinnett, D. Labuda, A. Moghrabi, and M. Krajinovic DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL Blood, April 1, 2008; 111(7): 3692 - 3700. [Abstract] [Full Text] [PDF] S. M. Davies, M. J. 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