Details

Autor(en) / Beteiligte

• Dufour, Annika
• Schneider, Friederike
• Hoster, Eva
• Benthaus, Tobias
• Ksienzyk, Bianka
• Schneider, Stephanie
• Kakadia, Purvi M.
• Sauerland, Maria-Cristina
• Berdel, Wolfgang E.
• Büchner, Thomas
• Wörmann, Bernhard
• Braess, Jan
• Subklewe, Marion
• Hiddemann, Wolfgang
• Bohlander, Stefan K.
• Spiekermann, Karsten

Titel

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

Ist Teil von

• Annals of hematology, 2012-07, Vol.91 (7), p.1051-1063

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2012

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• 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.