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Both inherited traits and tumor mutations affect response to treatment of leukemia

The outcome of chemotherapy treatment for acute lymphoblastic leukemia (ALL) depends not only on the acquired genetic make-up of the leukemic cells, but on genes that children inherit from their parents. This study, from investigators at St. Jude Children's Research Hospital, is published in the online edition of Blood.

The study provides strong evidence that it might be possible to design ALL treatment based in part on an individual patient's inherited genetic makeup. ALL is the most common tumor in children and affects the cells of the bone marrow. Currently, gene-based individualization of treatments is based only on the genetic mutations of leukemic cells. Chemotherapy must be more aggressive and may have more side effects if leukemic cells have genetics indicating a higher risk of relapse than if the leukemia cells indicate a lower risk of relapse. So-called germline (inherited) genetic characteristics are generally not used to identify children at high risk for relapse. But that could change because of the findings of this study, the researchers suggest.

The St. Jude team demonstrated that certain traits inherited from parents could reduce the effectiveness of some cancer chemotherapy. The findings therefore have the potential to improve treatment outcome by providing additional genetic clues that enable clinicians to identify patients at high or low risk of relapsing, according to Mary Relling, Pharm.D., chair of St. Jude Pharmaceutical Sciences and senior author of the Blood report.

"Therapy for ALL usually lasts two to three years," Relling said. "So over such a long period, even small changes that affect the potency of cancer drugs could have a major influence on the outcome of treatment."

The goal of the St. Jude study was to determine whether the success or failure of chemotherapy for ALL was linked to any of 16 common genetic polymorphisms in genes that interact with the ALL chemotherapy. Polymorphisms are slight variations in inher
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
2-Mar-2005


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