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Gene expression pattern predicts multiple drug resistance, treatment failure in pediatric leukemia

The discovery of a specific pattern of gene expression linked to multiple-drug resistance of leukemic cells is giving researchers crucial information into why standard therapies fail to cure some children with acute lymphoblastic leukemia (ALL). This finding, from investigators at St. Jude Children's Research Hospital, could lead to development of drugs that would overcome that resistance.

This new finding helps to explain why about 20 percent of children with ALL, the most common form of childhood cancer, are not cured with the same drug therapy that cures the remaining 80 percent of children with this disease. A report on the study that produced this new information appears in the April issue of Cancer Cell.

Drug resistance is a major cause of treatment failure, and the biochemical mechanisms responsible for de novo resistance are largely unknown. De novo resistance means that the resistance is "built into" the leukemic cells through a particular pattern of gene expression, rather than acquired through genetic mutation during treatment. Cross-resistance to multiple drugs suggests a poor prognosis and likely involves biochemical mechanisms that are different from those linked to single-drug resistance.

The investigators sought to identify the specific pattern of gene expression in ALL cells that is linked to de novo cross-resistance to four widely used antileukemic agents, and to determine how those genes affected treatment outcome.

"The identification of a particular genetic expression pattern linked to cross-resistance takes us a significant step forward in understanding why treatment fails to cure certain children who initially looked like good candidates for standard chemotherapy," said William E. Evans, Pharm.D., St. Jude director and member of St. Jude Pharmaceutical Sciences. "The results also give us crucial information into treatment failure that could help us design more effective treatments for the children our current treatment
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Contact: Carrie Strehlau
Carrie.Strehlau@stjude.org
901-495-3306
St. Jude Children's Research Hospital
18-Apr-2005


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