title: The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication.
abstract: Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA(+) de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapse-free, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P = .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA(+) AML (multivariate hazard ratio = 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively).
authors.affiliation: Department of Hematology, Hôpital Claude Huriez, Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gachard
authors.forename: Dina
authors.initials: D
authors.lastname: Naguib
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.forename: Stéphane
authors.initials: S
authors.lastname: de Botton
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.forename: Christine
authors.initials: C
authors.lastname: Terré
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D020440:Gene Duplication; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3