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Lancet. 2002 Mar 23;359(9311):1033-4.

Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukaemia.

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  • 1Service d'Hématologie-Oncologie, Centre de Recherche, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine, Quebec H3T 1C5, Montreal, Canada.


Interindividual variability in response to methotrexate could be caused by variable concentrations of thymidylate synthase. We investigated the possible association between a tandem-repeat polymorphism in the thymidylate synthase promoter, of which a triple repeat is associated with increased expression of thymidylate synthase, and outcome of acute lymphoblastic leukaemia in 205 children treated with methotrexate. We obtained DNA samples from buccal epithelial cells, peripheral blood, or bone marrow in remission, and analysed them for the polymorphism by PCR amplification. Individuals who were homozygous for the triple repeat had a poorer outlook than those with other genotypes (odds ratio 4.1, 95% CI 1.9-9.0, p=0.001). Genotyping of thymidylate synthase might make it possible to individualize treatment for patients with acute lymphoblastic leukaemia.

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