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Open Access Green as soon as Postprint is submitted to ZB.
Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: Independent favorable prognostic factor within NPM1 mutated patients.
Ann. Hematol. 91, 1051-1063 (2012)
We and others have shown that cytogenetically normal (CN)-AML patients with biallelic CEBPA gene mutations (biCEBPA) represent a molecularly distinct group with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation (moCEBPA), however, show no different outcome compared to patients with wildtype CEBPA, and these mutations are frequently associated with mutated NPM1 or FLT3-ITD. So far, no molecular or clinical hallmark has been identified to prognostically distinguish moCEBPA patients from patients with wildtype CEBPA. Therefore, we used the data of 663 CN-AML patients treated within the AMLCG 1999 trial to explore the prognostic value of moCEBPA in the context of concomitant clinical and molecular markers (mutated NPM1, FLT3-ITD). Multiple Cox regression in 515 patients adjusting for all available potential confounders revealed that the NPM1 mutation modified the prognostic value of moCEBPA with respect to overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011). MoCEBPA was beneficial in NPM1 mutated patients: adjusted OS-hazard ratio (HR) 0.09, 95% confidence interval (CI) 0.01-0.63, p = 0.016; EFS-HR (95% CI) 0.16 (0.04-0.65), p = 0.010. In contrast, moCEBPA had no prognostic impact in patients with wildtype NPM1: OS-HR (95% CI) 1.08 (0.59-1.97), p = 0.804; EFS-HR (95% CI) 1.12 (0.64-1.96), p = 0.682. We found no prognostic effect modification for moCEBPA by FLT3-ITD. The presence of a moCEBPA mutation was shown to be associated with prolonged survival in NPM1 mutated CN-AML patients. Confirmation of these results in larger studies will clarify whether an additional moCEBPA mutation influences the risk stratification of patients with an NPM1 mutated/FLT3-ITD positive genotype.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Monoallelic Cebpa Mutations; Npm1 Mutation; Normal Karyotype; Acute Myeloid Leukemia; INTERNAL TANDEM DUPLICATION; BINDING-PROTEIN-ALPHA; ACUTE MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; C/EBP-ALPHA; ADULT PATIENTS; NORMAL CYTOGENETICS; NUCLEOPHOSMIN NPM1; INITIATING CELLS; YOUNGER ADULTS
ISSN (print) / ISBN
0939-5555
e-ISSN
1432-0584
Journal
Annals of Hematology
Quellenangaben
Volume: 91,
Issue: 7,
Pages: 1051-1063
Publisher
Springer
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)