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Molecular science could further improve leukemia survival, say St. Jude researchers
Date:3/21/2008

ent genes in different cell types; and the other is pharmacogenetics. RNA is the decoded form of genes and is a signal that those genes have been active. Pharmacogenetics is the study of how genes influence a persons responses to drugs.

Although still in the research phase, profiling a cells RNA can identify the major subtypes of ALL and pinpoint genes or chemical signaling pathways that play a role in determining a patients outcome.

Gene expression profiling will help us identify targets for future therapy, Pui said. It is still crude, but in the end, you identify multiple genes for further study. If you find a good target for therapy, the next step is to develop molecular therapeutics for the target.

Even a slight change in a gene may affect the efficacy and toxic side effects of cancer drugs. Originally, researchers focused on the influence of single genes. Now they seek to learn how the combination of gene variations within a cell affects treatment.

Pharmacogenetics is important to finding out a persons response and tolerance for a therapy, Pui said. Certain drugs may be good for 99 percent of patients but bad for 1 percent. We need to find out who those patients are who are at risk so we can spare them from toxicity.

For instance, a genetic alteration affects an enzyme called thiopurine methyltransferase. Children with this alteration cannot metabolize a certain anti-cancer drug, and the active metabolite of the drug can accumulate in the body until it reaches toxic levels. About 10 percent of patients inherit one normal gene and one altered (non-functioning) gene for the enzyme, and one in 300 inherit two non-functioning versions of the gene.

Half of those with the one altered gene and all of those with two altered genes develop low blood cell counts when treated with regular dose of the drug, which can prove fatal in those with two altered genes. Determining the gene status of ALL patients can alert phys
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Contact: Summer Freeman
summer.freeman@stjude.org
901-435-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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