The enzyme thymidylate synthase is associated with cell proliferation, and is therefore an important target for anticancer drugs, including the chemotherapeutic agent methotrexate. Maja Krajinovic from the University of Montreal, Canada, and colleagues investigated the possible association between a variant of the gene coding for thymidylate synthase(in which a specific triple repeat alteration is associated with increased expression of thymidylate synthase) and the outcome of acute lymphoblastic leukaemia in 205 children treated with methotrexate.
DNA samples from patients were analysed for variation by polymerase chain reaction (PCR) amplification. Children who were homozygous for the triple repeat were four times more likely to have a poorer outcome than children with other genotypes.
Maja Krajinovic comments: “Thymidylate synthase genotype seems to be a significant predictor of outcome in childhood acute lymphoblastic leukaemia. This finding could lead to individualisation of treatment for patients with this disease.”
Contact: Dr Maja Krajinovic, Département de Pédiatrie, Université de Montréal, Montréal, Canada ; T) +1 514 345 6259; F) +1 514 345 4731 ; E) maja.krajinovic@umontreal.ca
Journal
The Lancet