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- Title
Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients.
- Authors
Dufour, Annika; Schneider, Friederike; Hoster, Eva; Benthaus, Tobias; Ksienzyk, Bianka; Schneider, Stephanie; Kakadia, Purvi; Sauerland, Maria-Cristina; Berdel, Wolfgang; Büchner, Thomas; Wörmann, Bernhard; Braess, Jan; Subklewe, Marion; Hiddemann, Wolfgang; Bohlander, Stefan; Spiekermann, Karsten
- Abstract
We and others have shown that cytogenetically normal (CN)-AML patients with biallelic CEBPA gene mutations (bi CEBPA) represent a molecularly distinct group with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation (mo CEBPA), 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 mo CEBPA 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 mo CEBPA 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 mo CEBPA with respect to overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011). Mo CEBPA 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, mo CEBPA 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 mo CEBPA by FLT3-ITD. The presence of a mo CEBPA 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 mo CEBPA mutation influences the risk stratification of patients with an NPM1 mutated/ FLT3-ITD positive genotype.
- Subjects
GENETIC mutation; MYELOID leukemia; CHROMOSOME abnormalities; REGRESSION analysis; MEDICAL statistics; DATA analysis
- Publication
Annals of Hematology, 2012, Vol 91, Issue 7, p1051
- ISSN
0939-5555
- Publication type
Article
- DOI
10.1007/s00277-012-1423-4