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St. Jude Gene Study Reveals Basis of Anti-Cancer Drug Resistance in Childhood Leukemia
Date:4/15/2008

e genes in the patient samples.

"In our analysis, we identified a large number of genes in the treated patients that differed in their expression level at a very significant level statistically," Evans said. "We elected to focus on the 50 most highly significant genes."

Among the genes were those involved in DNA synthesis, its components and repair of DNA. The identity of some of these genes was not surprising because the drug kills leukemia cells by interfering with their ability to replicate their DNA.

When the researchers compared the gene expression patterns of patients who responded well to methotrexate to those who responded poorly, they found distinct gene expression "profiles" among the groups. In further analysis to validate their findings, they found that the profiles predicted methotrexate response in an independent group of patients: Patients with gene expression profiles indicating a good methotrexate response had significantly better five-year, disease-free survival than those with profiles indicating a poor response.

To confirm their findings, the researchers also analyzed the predictive effects of those distinctive profiles in an independent group of 18 patients. They found that the gene expression profiles for the top 50 genes also predicted methotrexate response in those patients.

Further exploration of the genes identified in this study could yield clinical benefits. "Some of these could become potential targets for developing other drugs that would make methotrexate more effective in those children who are resistant," Evans said.

For example, one gene they identified as relevant to resistance produces a protein that transports the drug out of the leukemia cell. "It might be possible to give a drug along with methotrexate that blocks this transporter, which would make methotrexate more effective without having to give another cytotoxic drug," Evans said.

In further studies, the researc
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SOURCE St. Jude Children's Research Hospital
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