Marker for Unfavorable Leukemia Prognosis

Genetic testing for an enzyme involved in cancer-cell proliferation could identify patients at an increased risk of poor outcome from acute lymphoblastic leukemia.

A research letter in the March 23, 2002, issue of The Lancet reports that the enzyme thymidylate synthase is associated with cell proliferation, and is therefore an important target for anticancer drugs, including the chemotherapeutic agent methotrexate. The letter's author, Dr. 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 leukemia in 205 children treated with methotrexate.

DNA samples from patients were analyzed for variation by polymerase chain reaction (PCR) amplification. The results showed that children who were homozygous for the triple repeat were four times more likely to have a poorer outcome than children with other genotypes.

Dr. Krajinovic comments: "Thymidylate synthase genotype seems to be a significant predictor of outcome in childhood acute lymphoblastic leukemia. This finding could lead to individualization of treatment for patients with this disease.”




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