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Outcome for acute lymphoblastic leukemia linked to gene expression patterns

A relatively small number of genes are linked to either resistance or sensitivity to four major cancer drugs used to treat acute lymphoblastic leukemia (ALL), suggesting that these genes are key to treatment outcome. This study, by investigators from St. Jude Children's Research Hospital and Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands, is published in the Aug. 4, 2004 issue of the New England Journal of Medicine (NEJM).

The researchers identified four groups of genes, each of which had a characteristic pattern of expression in leukemia cells depending on whether they were sensitive or resistant to four widely used antileukemic agents. Investigators found that the expression pattern of these genes was significantly related to treatment outcome.

The study identified 123 previously unrecognized genes that are associated with resistance to cancer chemotherapy. Only three of these genes had been previously linked to drug resistance. These new genes represent potential targets for new agents that could be developed to overcome resistance to drugs currently used to treat ALL.

Despite the pioneering role of St. Jude in increasing the cure rate of childhood ALL from 4 percent to more than 80 percent during the past 40 years, the cause of failure in the remaining 20 percent of children is largely unknown, according to William E. Evans, Pharm.D., St. Jude scientific director. The current findings could help further reduce the number of failures. Evans is a senior author of the NEJM report.

"We've known for years that certain genetic changes in leukemic cells are associated with a high risk of treatment failure," Evans said. "But we also realized that many children who have an unfavorable genetic subtype of ALL are cured, and many patients whose genetic subtype was considered to be favorable weren't cured. The findings of this study are helping us understand
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
4-Aug-2004


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