title: Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.
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.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Eng-Juh
authors.initials: EJ
authors.lastname: Yeoh
authors.forename: Mary E
authors.initials: ME
authors.lastname: Ross
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Shurtleff
authors.forename: W Kent
authors.initials: WK
authors.lastname: Williams
authors.forename: Divyen
authors.initials: D
authors.lastname: Patel
authors.forename: Rami
authors.initials: R
authors.lastname: Mahfouz
authors.forename: Fred G
authors.initials: FG
authors.lastname: Behm
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.forename: Anami
authors.initials: A
authors.lastname: Patel
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
authors.forename: Dawn
authors.initials: D
authors.lastname: Wilkins
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Jinyan
authors.initials: J
authors.lastname: Li
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
authors.forename: Clayton
authors.initials: C
authors.lastname: Naeve
authors.forename: Limsoon
authors.initials: L
authors.lastname: Wong
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
mesh_terms: D000465:Algorithms; D002648:Child; D019295:Computational Biology; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D017211:Treatment Failure