Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.
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.
Yeoh
Eng-Juh
EJ
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ross
Mary E
ME
Shurtleff
Sheila A
SA
Williams
W Kent
WK
Patel
Divyen
D
Mahfouz
Rami
R
Behm
Fred G
FG
Raimondi
Susana C
SC
Relling
Mary V
MV
Patel
Anami
A
Cheng
Cheng
C
Campana
Dario
D
Wilkins
Dawn
D
Zhou
Xiaodong
X
Li
Jinyan
J
Liu
Huiqing
H
Pui
Ching-Hon
CH
Evans
William E
WE
Naeve
Clayton
C
Wong
Limsoon
L
Downing
James R
JR
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