title: Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group.
abstract: 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA. pho@fhcrc.org
authors.forename: Phoenix A
authors.initials: PA
authors.lastname: Ho
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Jessica
authors.initials: J
authors.lastname: Pollard
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Craig
authors.initials: C
authors.lastname: Hurwitz
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Betsy
authors.initials: B
authors.lastname: Hirsch
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Beverly
authors.initials: B
authors.lastname: Lange
authors.forename: Janet L
authors.initials: JL
authors.lastname: Franklin
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D011379:Prognosis; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins