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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4871-4879. Prepublished online as a Blood First Edition Paper on February 28, 2006; DOI 10.1182/blood-2005-08-3272. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3272v1 107/12/4871    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 Monzo, M. Articles by Sierra, J. Search for Related Content PubMed PubMed Citation Articles by Monzo, M. Articles by Sierra, J. Related Collections Genomics Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia Mariano Monzo, Salut Brunet, Alvaro Urbano-Ispizua, Alfons Navarro, Granada Perea, Jordi Esteve, Rosa Artells, Miquel Granell, Juan Berlanga, Josep M. Ribera, Javier Bueno, Andreu Llorente, Ramon Guardia, Mar Tormo, Pio Torres, Josep F. Nomdedéu, Emili Montserrat, Jordi Sierra, for CETLAM From the Hospital Clínic, Hospital Universitario de la Santa Creu i Sant Pau, Hospital de la Vall d'Hebrón, Barcelona; Hospital Germans Trias i Pujol, Badalona; Institut Català d'Oncología, Hospitalet de Llobregat, Hospitalet; Hospital Joan XXIII, Tarragona; Hospital Clínico, Valencia; Hospital Juan Canalejo, ACoruña; Hospital Dr Josep Trueta, Girona; and Department of Human Anatomy, Faculty of Medicine, University of Barcelona, Barcelona, Spain. Current prognostic factors for acute myeloblastic leukemia (AML) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment. Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses. We used the allelic discrimination method to identify polymorphisms in GSTT1, SULT1C2, CDA, SXR (drug metabolic pathways), XPD, XPA, XPG, ERCC1, TOP2A (DNA repair), VEGF (angiogenesis), and MDR1 (multidrug resistance) genes in 110 adult patients with intermediate-risk AML, enrolled in the CETLAM-99 prospective trial. A multivariate prognostic model adjusted for age, white blood cell (WBC) count, French-American-British group, cytogenetics, MLL rearrangement, internal tandem duplication of FLT3 (FLT3-ITD), induction courses to achieve complete remission, and germline polymorphisms, was used to detect independent risk factors associated with clinical outcome. This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles (RR = 14; P = .02). In the same model, increased relapse risk was associated with SULT1C2 heterozygosity (RR = 4.1; P = .004), FLT3-ITD (RR 3.3; P = .003), and MDR1 variant alleles (RR = 2.4; P = .02). Adverse prognostic variables for overall survival were XPA (RR = 3.4; P = .02) and MDR1 (RR = 2.1; P = .02) variant alleles, and WBC count (RR = 2.1; P = .02). These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Hopkins, D. W. Cescon, D. Tse, P. Bradbury, W. Xu, C. Ma, P. Wheatley-Price, J. Waldron, D. Goldstein, F. Meyer, et al. Genetic Polymorphisms and Head and Neck Cancer Outcomes: A Review Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 490 - 499. [Abstract] [Full Text] [PDF]

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