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Erschienen in: Annals of Hematology 7/2012

01.07.2012 | Original Article

Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients

verfasst von: Annika Dufour, Friederike Schneider, Eva Hoster, Tobias Benthaus, Bianka Ksienzyk, Stephanie Schneider, Purvi M. Kakadia, Maria-Cristina Sauerland, Wolfgang E. Berdel, Thomas Büchner, Bernhard Wörmann, Jan Braess, Marion Subklewe, Wolfgang Hiddemann, Stefan K. Bohlander, Karsten Spiekermann, for the AML CG study group

Erschienen in: Annals of Hematology | Ausgabe 7/2012

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Abstract

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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Metadaten
Titel
Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients
verfasst von
Annika Dufour
Friederike Schneider
Eva Hoster
Tobias Benthaus
Bianka Ksienzyk
Stephanie Schneider
Purvi M. Kakadia
Maria-Cristina Sauerland
Wolfgang E. Berdel
Thomas Büchner
Bernhard Wörmann
Jan Braess
Marion Subklewe
Wolfgang Hiddemann
Stefan K. Bohlander
Karsten Spiekermann
for the AML CG study group
Publikationsdatum
01.07.2012
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 7/2012
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-012-1423-4

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