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

Huining Kang, I. Ming Chen, Carla S. Wilson, Edward J. Bedrick, Richard C. Harvey, Susan R. Atlas, Meenakshi Devidas, Charles G. Mullighan, Xuefei Wang, Maurice Murphy, Kerem Ar, Walker Wharton, Michael J. Borowitz, W. Paul Bowman, Deepa Bhojwani, William L. Carroll, Bruce M. Camitta, Gregory H. Reaman, Malcolm A. Smith, James R. DowningStephen P. Hunger, Cheryl L. Willman

Research output: Contribution to journalArticlepeer-review

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 highrisk ALL cohort (P = .006) and retained independent 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.

Original languageEnglish (US)
Pages (from-to)1394-1405
Number of pages12
JournalBlood
Volume115
Issue number7
DOIs
StatePublished - Feb 18 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this