Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group

Blood. 2009 Jun 25;113(26):6558-66. doi: 10.1182/blood-2008-10-184747. Epub 2009 Mar 20.


CEBPA mutations have been associated with improved outcome in adult acute myeloid leukemia (AML). We evaluated the prevalence and prognostic significance of CEBPA mutations in 847 children with AML treated on 3 consecutive pediatric trials. Two types of CEBPA mutations-N-terminal truncating mutations and in-frame bZip-domain mutations-were detected in 38 (4.5%) of 847 patients tested; 31 (82%) of 38 patients with mutations harbored both mutation types. Mutation status was correlated with laboratory and clinical characteristics and clinical outcome. CEBPA mutations were significantly more common in older patients, patients with FAB M1 or M2, and patients with normal karyotype. Mutations did not occur in patients with either favorable or unfavorable cytogenetics. Actuarial event-free survival at 5 years was 70% versus 38% (P = .015) with a cumulative incidence of relapse from complete remission of 13% versus 44% (P = .007) for those with and without CEBPA mutations. The presence of CEBPA mutations was an independent prognostic factor for improved outcome (HR = 0.24, P = .047). As CEBPA mutations are associated with lower relapse rate and improved survival, CEBPA mutation analysis needs to be incorporated into initial screening for risk identification and therapy allocation at diagnosis.

Trial registration: NCT00002798 NCT00070174.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adolescent
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / physiology
  • Child
  • Child, Preschool
  • Clinical Trials as Topic / statistics & numerical data
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / mortality
  • Male
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Polymorphism, Genetic
  • Prevalence
  • Prognosis
  • Protein Structure, Tertiary
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • DNA, Neoplasm
  • Neoplasm Proteins

Associated data