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Dufour, A.* ; Schneider, F.* ; Hoster, E.* ; Benthaus, T.* ; Ksienzyk, B.* ; Schneider, S.* ; Kakadia, P.M.* ; Sauerland, M.C.* ; Berdel, W.E.* ; Büchner, T.* ; Wörmann, B.* ; Braess, J.* ; Subklewe, M.* ; Hiddemann, W. ; Bohlander, S.K. ; Spiekermann, K.

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

Ann. Hematol. 91, 1051-1063 (2012)
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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
Language
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0939-5555
e-ISSN 1432-0584
Journal Annals of Hematology
Quellenangaben Volume: 91, Issue: 7, Pages: 1051-1063 Article Number: , Supplement: ,
Publisher Springer
Reviewing status Peer reviewed
Institute(s) CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-521000-001
PubMed ID 22362118
DOI 10.1007/s00277-012-1423-4
WOS ID WOS:000304874700008
Scopus ID 84862762733
Erfassungsdatum 2012-06-28
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