Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Academic Article uri icon

start page

  • 1394

end page

  • 1405

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.

date/time value

  • 2010

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-05-218560

PubMed Identifier

  • 19880498

volume

  • 115

number

  • 7

keywords

  • 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