March 2002

From Lancet

Genetic test for cell-proliferation enzyme could improve treatment of acute lymphoblastic leukaemia

N.B. Please note that if you are outside North America the embargo date for all Lancet press material is 0001hours UK time Friday 22nd March 2002

Authors of a Canadian research letter in this week's issue of THE LANCET describe how genetic testing for an enzyme involved in cancer-cell proliferation could identify patients at an increased risk of poor outcome from acute lymphoblastic leukaemia.

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, D�partement de P�diatrie, Universit� de Montr�al, Montr�al, Canada ; T) +1 514 345 6259; F) +1 514 345 4731 ; E) [email protected]



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