Faculty Collaboration Database

Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood 2010 Feb 18;115(7):1394-405

Date

11/03/2009

Pubmed ID

19880498

Pubmed Central ID

PMC2826761

DOI

10.1182/blood-2009-05-218560

Scopus ID

2-s2.0-77949879862 (requires institutional sign-in at Scopus site)   171 Citations

Abstract

To determine whether gene expression profiling could improve outcome prediction in children with acute lymphoblastic leukemia (ALL) at high risk for relapse, we profiled pretreatment leukemic cells in 207 uniformly treated children with high-risk B-precursor ALL. A 38-gene expression classifier predictive of relapse-free survival (RFS) could distinguish 2 groups with differing relapse risks: low (4-year RFS, 81%, n = 109) versus high (4-year RFS, 50%, n = 98; P < .001). In multivariate analysis, the gene expression classifier (P = .001) and flow cytometric measures of minimal residual disease (MRD; P = .001) each provided independent prognostic information. Together, they could be used to classify children with high-risk ALL into low- (87% RFS), intermediate- (62% RFS), or high- (29% RFS) risk groups (P < .001). A 21-gene expression classifier predictive of end-induction MRD effectively substituted for flow MRD, yielding a combined classifier that could distinguish these 3 risk groups at diagnosis (P < .001). These classifiers were further validated on an independent high-risk ALL cohort (P = .006) and retainedindependent prognostic significance (P < .001) in the presence of other recently described poor prognostic factors (IKAROS/IKZF1 deletions, JAK mutations, and kinase expression signatures). Thus, gene expression classifiers improve ALL risk classification and allow prospective identification of children who respond or fail current treatment regimens. These trials were registered at http://clinicaltrials.gov under NCT00005603.

Author List

Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, Devidas M, Mullighan CG, Wang X, Murphy M, Ar K, Wharton W, Borowitz MJ, Bowman WP, Bhojwani D, Carroll WL, Camitta BM, Reaman GH, Smith MA, Downing JR, Hunger SP, Willman CL

Author

Bruce m. Camitta Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Child
Child, Preschool
Female
Flow Cytometry
Gene Expression Regulation, Leukemic
Genetic Testing
Humans
Ikaros Transcription Factor
Infant
Janus Kinases
Kaplan-Meier Estimate
Male
Neoplasm, Residual
Oligonucleotide Array Sequence Analysis
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Predictive Value of Tests
Proportional Hazards Models
Recurrence
Reproducibility of Results
Risk Factors
Treatment Outcome
Young Adult