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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-01-0228. This Article Full Text (PDF) All Versions of this Article: 2002-01-0228v1 101/7/2770    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 Bowen, D. T Articles by Morgan, G. J Search for Related Content PubMed PubMed Citation Articles by Bowen, D. T Articles by Morgan, G. J Social Bookmarking                   What's this? Submitted January 25, 2002 Accepted November 13, 2002 Cytochrome P450 1A1 *2B (Val) allele is over-represented in a sub-group of acute myeloid leukemia patients with poor-risk karyotype associated with NRAS mutation, but not associated with FLT3 internal tandem duplication David T Bowen*, Marion E Frew, Sara Rollinson, Philippa L Roddam, Ann Dring, Martyn T Smith, Steven E Langabeer, and Gareth J Morgan Molecular and Cellular Pathology, Ninewells Hospital, Dundee, United Kingdom Academic Unit of Hematology and Oncology, University of Leeds, Leeds, United Kingdom School of Public Health, University of California, Berkeley, CA, USA Hematology, University College London, London, United Kingdom * Corresponding author; email: d.t.bowen{at}dundee.ac.uk. The etiology of acute myeloid leukemia (AML) is largely unknown. Biological and epidemiological data implicate exogenous toxicants including cytotoxic drugs, benzene, radiation and cigarette smoking. Allelic variation in genes encoding enzymes such as NADP(H) quinone oxidoreductase and glutathione S-transferase T1 that metabolise environmental toxicants predispose to sub-types of AML including therapy-related AML. We assayed NRAS oncogene mutation and FLT3 internal tandem duplication in 447 AML patients selected for an abnormal karyotype from those treated within the MRC AML 10, 11 and 12 clinical trials. Functional allelic variant frequencies in genes encoding carcinogen-metabolising enzymes GSTT1, GSTM1, CYP1A1, CYP2D6, CYP2C19, SULT1A1 and NQO1 were previously determined for this cohort. FLT3 ITD frequency was 17% and NRAS mutation 12% for the entire selected cohort. Both mutations were found together in only 4 patients. No association was found between enzyme allelic variant frequencies and the presence of FLT3 ITD for the entire cohort or within cytogenetic subgroups. CYP1A1*2B (Val) high-inducibility variant allele was over-represented in patients with NRAS mutation compared with no mutation for a) the entire AML cohort (n=8/53 vs. 26/371; OR=2.36, 95%CI 1.01-5.53), and b) the poor-risk karyotype group comprising patients with partial/complete deletion of chromosome 5 or 7, or abnormalities of chromosome 3 (n=6/14 vs. 4/89; OR=15.94, 95%CI 3.71-68.52). The CYP1A1*2B allele may predispose to the development of these sub-groups of AML by augmented phase 1 metabolism to highly reactive intermediates of CYP1A1 substrates including polycyclic aromatic hydrocarbons or by generation of oxidative stress as a metabolic by-product. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Neubauer, K. Maharry, K. Mrozek, C. Thiede, G. Marcucci, P. Paschka, R. J. Mayer, R. A. Larson, E. T. Liu, and C. D. 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