Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report

Blood. 2017 Jun 8;129(23):3051-3058. doi: 10.1182/blood-2017-03-772384. Epub 2017 Apr 14.

Abstract

Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs) and determine their associations with treatment outcome. Data from Affymetrix and Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring altered genomic regions were identified, and the presence of CNAs was found to be associated with decreased 3-year overall survival (OS), event-free survival (EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI, 1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI, 1.1-2.6, respectively). Additional studies are required to test the prognostic significance of CNA presence in disease relapse in patients with AML. COG studies AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials.gov as #NCT01407757, #NCT00070174, and #NCT00003790, respectively.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Copy Number Variations*
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Treatment Outcome

Substances

  • DNA, Neoplasm
  • Genetic Markers

Associated data

  • ClinicalTrials.gov/NCT01407757
  • ClinicalTrials.gov/NCT00070174
  • ClinicalTrials.gov/NCT00003790
  • ClinicalTrials.gov/NCT01407757
  • ClinicalTrials.gov/NCT00070174
  • ClinicalTrials.gov/NCT00003790