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Prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group.

Abstract
CCAAT/enhancer-binding protein alpha (CEBPA) mutations are a favorable prognostic factor in adult acute myeloid leukemia (AML) patients; however, few studies have examined their significance in pediatric AML patients. Here we examined the CEBPA mutation status and clinical outcomes of pediatric AML patients treated in the AML-05 study. We found that 47 (14.9%) of the 315 evaluable patients harbored mutations in CEBPA; 26 cases (8.3%) harbored a single mutation (CEBPA-single) and 21 (6.7%) harbored double or triple mutations (CEBPA-double). After excluding core-binding factor-AML cases, patients harboring CEBPA mutations showed better overall survival (OS; P=0.048), but not event-free survival (EFS; P=0.051), than wild-type patients. Multivariate analysis identified CEBPA-single and CEBPA-double as independent favorable prognostic factors for EFS in the total cohort (hazard ratio (HR): 0.47 and 0.33; P=0.02 and 0.01, respectively). CEBPA-double was also an independent favorable prognostic factor for OS (HR: 0.30; P=0.04). CEBPA-double remained an independent favorable factor for EFS (HR: 0.28; P=0.04) in the normal karyotype cohort. These results suggest that CEBPA mutations, particularly CEBPA-double, are an independent favorable prognostic factor in pediatric AML patients, which will have important implications for risk-stratified therapy.
AuthorsH Matsuo, M Kajihara, D Tomizawa, T Watanabe, A M Saito, J Fujimoto, K Horibe, K Kodama, M Tokumasu, H Itoh, H Nakayama, A Kinoshita, T Taga, A Tawa, T Taki, S Tanaka, S Adachi
JournalBlood cancer journal (Blood Cancer J) Vol. 4 Pg. e226 (Jul 11 2014) ISSN: 2044-5385 [Print] United States
PMID25014773 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
Topics
  • Adolescent
  • CCAAT-Enhancer-Binding Proteins (genetics)
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute (genetics)
  • Male
  • Mutation
  • Polymorphism, Genetic
  • Prognosis

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