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.
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).
Renneville
Aline
A
Department of Hematology, Hôpital Claude Huriez, Lille, France.
Boissel
Nicolas
N
Gachard
Nathalie
N
Naguib
Dina
D
Bastard
Christian
C
de Botton
Stéphane
S
Nibourel
Olivier
O
Pautas
Cécile
C
Reman
Oumedaly
O
Thomas
Xavier
X
Gardin
Claude
C
Terré
Christine
C
Castaigne
Sylvie
S
Preudhomme
Claude
C
Dombret
Hervé
H
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*
D022763:CCAAT-Enhancer-Binding Protein-alpha; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3