Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia : independent favorable prognostic factor within NPM1 mutated patients
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:91 |
|---|---|
| Enthalten in: |
Annals of hematology - 91(2012), 7 vom: 22. Juli, Seite 1051-63 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dufour, Annika [VerfasserIn] |
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| Links: |
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| Themen: |
117896-08-9 |
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| Anmerkungen: |
Date Completed 09.08.2012 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00277-012-1423-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM215687272 |
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| 100 | 1 | |a Dufour, Annika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia |b independent favorable prognostic factor within NPM1 mutated patients |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a CCAAT-Enhancer-Binding Proteins |2 NLM | |
| 650 | 7 | |a CEBPA protein, human |2 NLM | |
| 650 | 7 | |a NPM1 protein, human |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Nucleophosmin |2 NLM | |
| 650 | 7 | |a 117896-08-9 |2 NLM | |
| 700 | 1 | |a Schneider, Friederike |e verfasserin |4 aut | |
| 700 | 1 | |a Hoster, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Benthaus, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Ksienzyk, Bianka |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Kakadia, Purvi M |e verfasserin |4 aut | |
| 700 | 1 | |a Sauerland, Maria-Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Berdel, Wolfgang E |e verfasserin |4 aut | |
| 700 | 1 | |a Büchner, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Wörmann, Bernhard |e verfasserin |4 aut | |
| 700 | 1 | |a Braess, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Subklewe, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Hiddemann, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Bohlander, Stefan K |e verfasserin |4 aut | |
| 700 | 1 | |a Spiekermann, Karsten |e verfasserin |4 aut | |
| 700 | 0 | |a AML CG study group |e verfasserin |4 aut | |
| 700 | 1 | |a Büchner, T |e investigator |4 oth | |
| 700 | 1 | |a Hiddemann, W |e investigator |4 oth | |
| 700 | 1 | |a Berdel, W E |e investigator |4 oth | |
| 700 | 1 | |a Wörmann, B |e investigator |4 oth | |
| 700 | 1 | |a Heinecke, A |e investigator |4 oth | |
| 700 | 1 | |a Sauerland, M C |e investigator |4 oth | |
| 700 | 1 | |a Schneider, F |e investigator |4 oth | |
| 700 | 1 | |a Hoster, E |e investigator |4 oth | |
| 700 | 1 | |a Unterhalt, M |e investigator |4 oth | |
| 700 | 1 | |a Haferlach, C |e investigator |4 oth | |
| 700 | 1 | |a Schnittger, S |e investigator |4 oth | |
| 700 | 1 | |a Kakadia, P M |e investigator |4 oth | |
| 700 | 1 | |a Bohlander, S K |e investigator |4 oth | |
| 700 | 1 | |a Dufour, A |e investigator |4 oth | |
| 700 | 1 | |a Spiekermann, K |e investigator |4 oth | |
| 700 | 1 | |a Haferlach, T |e investigator |4 oth | |
| 700 | 1 | |a Braess, J |e investigator |4 oth | |
| 700 | 1 | |a Spiekermann, K |e investigator |4 oth | |
| 700 | 1 | |a Ittel, T H |e investigator |4 oth | |
| 700 | 1 | |a Schmid, C |e investigator |4 oth | |
| 700 | 1 | |a Oruzio, D |e investigator |4 oth | |
| 700 | 1 | |a Fu, H |e investigator |4 oth | |
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| 700 | 1 | |a Notter, M |e investigator |4 oth | |
| 700 | 1 | |a Thiel, E |e investigator |4 oth | |
| 700 | 1 | |a Ludwig, W D |e investigator |4 oth | |
| 700 | 1 | |a Schöndube, D |e investigator |4 oth | |
| 700 | 1 | |a Späth-Schwalbe, E |e investigator |4 oth | |
| 700 | 1 | |a Hesse, S |e investigator |4 oth | |
| 700 | 1 | |a Grüneisen, A |e investigator |4 oth | |
| 700 | 1 | |a Potenberg, J |e investigator |4 oth | |
| 700 | 1 | |a Weh, A J |e investigator |4 oth | |
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| 700 | 1 | |a Niederste-Hollenberg, A |e investigator |4 oth | |
| 700 | 1 | |a Pielken, H |e investigator |4 oth | |
| 700 | 1 | |a Hindahl, H |e investigator |4 oth | |
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