title: 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.
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Department of Nutritional Science, Aichi Gakuin University, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: A M
authors.initials: AM
authors.lastname: Saito
authors.affiliation: Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Fujimoto
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.affiliation: Department of Pediatrics, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tokumasu
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Pediatrics, National Hospital Organization Fukuoka-Higashi Medical Center, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, St Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taga
authors.affiliation: Department of Pediatrics, National Hospital Organization Osaka Medical Hospital, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.affiliation: Department of Pharmacoepidemiology, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Adachi
mesh_terms: D000293:Adolescent; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human