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St. Jude gene study reveals basis of anticancer drug resistance in childhood leukemia
Date:4/15/2008

The first analysis of the genetic determinants of resistance to the anti-cancer drug methotrexate in childhood acute lymphoblastic leukemia (ALL) could offer a pathway to predicting such resistance and treatments to overcome it, according to a St. Jude Childrens Research Hospital study.

Besides its use in ALL, methotrexate is widely used to treat other cancers and some autoimmune diseases. However, until the new study there was no valid test for analyzing the genetic basis of resistance. Such genetic analysis is important in childhood ALL because, although 80 percent of children with the disease can be cured, determining the basis of drug resistance in the other 20 percent would help increase the cure rate.

The researchers, led by Dr. William E. Evans, St. Jude hospital director and member of St. Jude Pharmaceutical Sciences, reported their findings in the April 2008 issue of PLoS Medicine.

Researchers have successfully used laboratory studies of leukemia cells to explore the basis of resistance in other anti-leukemia drugs. However, according to Evans, such in vitro tests have not worked with methotrexate. The researchers analyzed the genetic profiles of St. Jude patients undergoing methotrexate treatment for ALL to identify genes that governed their response to the drug.

In their study of 161 ALL patients, they measured the response to initial methotrexate treatment and then used gene microarray analysis to measure the activity levels of 12,357 genes in the patients. In microarray analysis, researchers apply genetic material from the patients leukemia cells to small gene chips on which samples of thousands of genes are arrayed. Researchers can analyze the reactions on the gene chip to each gene to measure the level of expression for those 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 st
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Contact: Carrie Strehlau
media@stjude.org
901-495-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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