Classification,subtype discovery,and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling |
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Authors: | Yeoh Eng-Juh Ross Mary E Shurtleff Sheila A Williams W Kent Patel Divyen Mahfouz Rami Behm Fred G Raimondi Susana C Relling Mary V Patel Anami Cheng Cheng Campana Dario Wilkins Dawn Zhou Xiaodong Li Jinyan Liu Huiqing Pui Ching-Hon Evans William E Naeve Clayton Wong Limsoon Downing James R |
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Affiliation: | Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. |
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Abstract: | Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the prognostically important leukemia subtypes, including T-ALL, E2A-PBX1, BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes. In addition, another ALL subgroup was identified based on its unique expression profile. Examination of the genes comprising the expression signatures provided important insights into the biology of these leukemia subgroups. Further, within some genetic subgroups, expression profiles identified those patients that would eventually fail therapy. Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients. |
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