Gene Expression Profiling and the Treatment of Pediatric Acute Lymphoblastic Leukemia
Washington, D.C. - New gene expression profiling studies may offer novel therapeutic directions for children with acute lymphoblastic leukemia (ALL). Allen Eng-Juh Yeoh, M.D., from St. Jude Children's Research Hospital, presented these findings at the 43rd Annual Meeting of the American Society of Hematology (ASH), held December 7-11, in Orlando, Florida.
Childhood ALL is a genetic disease. Mutant genes result in uncontrolled growth of leukemia cells. This growth prevents bone marrow from producing normal blood cells, culminating in infection, anemia and bleeding - the hallmarks of leukemia.
Relapse remains the major cause of treatment failure for children diagnosed with pediatric ALL. Gene expression profiling may improve treatment by more accurately predicting those who are at risk of relapse than currently used predictors. Recent technological advances have allowed scientists to use microchip arrays to sample messages emanating from the nucleus of cells. In the present study, researchers from St. Jude simultaneously measured the levels of 12,000 different messenger RNA in leukemic cells from different types of childhood ALL. They were able to identify several different message profiles (or expression profiles) that define the important subgroups of childhood ALL and predict the subgroups with accuracy exceeding 95 percent, thereby suggesting the utility of this new technique as a diagnostic tool.
Childhood ALL is a heterogeneous disease. Therapy refinement by precise risk-stratification is increasingly important not only to avoid overtreatment of patients who are at low risk of relapse, but also to ensure adequate treatment of those at high risk of relapse. At present patients are assigned to risk groups using imperfect features that do not accurately predict the risk of relapse. "The use of genetic sampling will greatly improve the capacity to provide more accurate risk prediction," said Dr. Yeoh.
Then, by altering the intensity of therapy based on the relapse risk, doctors can help maximize the risk-benefit ratio of treatment and reserve the more intensive treatment for high-risk patients.
In addition to providing important new clinical information, expression profiling also allows scientists to better understand the underlying biology of different leukemia subgroups, and provides new insights into the causes of treatment failures. Remarkably, the use of expression profiling in childhood ALL allowed the prediction of treatment-related cancers arising as a side effect of treatment in the most common subgroup of patients. This suggests that expression profiling of leukemia cells at diagnosis will significantly improve therapy in children with ALL.
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