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CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome

Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study All...

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Hauptverfasser: Taube, Franziska (VerfasserIn) , Georgi, Julia Annabell (VerfasserIn) , Kramer, Michael (VerfasserIn) , Stasik, Sebastian (VerfasserIn) , Middeke, Jan Moritz (VerfasserIn) , Röllig, Christoph (VerfasserIn) , Krug, Utz (VerfasserIn) , Krämer, Alwin (VerfasserIn) , Scholl, Sebastian (VerfasserIn) , Hochhaus, Andreas (VerfasserIn) , Brümmendorf, Tim H. (VerfasserIn) , Naumann, Ralph (VerfasserIn) , Petzold, Andreas (VerfasserIn) , Mulet-Lazaro, Roger (VerfasserIn) , Valk, Peter J. M. (VerfasserIn) , Steffen, Björn (VerfasserIn) , Einsele, Hermann (VerfasserIn) , Schaich, Markus (VerfasserIn) , Burchert, Andreas (VerfasserIn) , Neubauer, Andreas (VerfasserIn) , Schäfer-Eckart, Kerstin (VerfasserIn) , Schliemann, Christoph (VerfasserIn) , Krause, Stefan W. (VerfasserIn) , Hänel, Mathias (VerfasserIn) , Noppeney, Richard (VerfasserIn) , Kaiser, Ulrich (VerfasserIn) , Baldus, Claudia D. (VerfasserIn) , Kaufmann, Martin (VerfasserIn) , Herold, Sylvia (VerfasserIn) , Stölzel, Friedrich (VerfasserIn) , Sockel, Katja (VerfasserIn) , von Bonin, Malte (VerfasserIn) , Müller-Tidow, Carsten (VerfasserIn) , Platzbecker, Uwe (VerfasserIn) , Berdel, Wolfgang E. (VerfasserIn) , Serve, Hubert (VerfasserIn) , Ehninger, Gerhard (VerfasserIn) , Bornhäuser, Martin (VerfasserIn) , Schetelig, Johannes (VerfasserIn) , Thiede, Christian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 6 January 2022
In: Blood
Year: 2022, Jahrgang: 139, Heft: 1, Pages: 87-103
ISSN:1528-0020
DOI:10.1182/blood.2020009680
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Verfasserangaben:Franziska Taube, Julia Annabell Georgi, Michael Kramer, Sebastian Stasik, Jan Moritz Middeke, Christoph Röllig, Utz Krug, Alwin Krämer, Sebastian Scholl, Andreas Hochhaus, Tim H. Brümmendorf, Ralph Naumann, Andreas Petzold, Roger Mulet-Lazaro, Peter J.M. Valk, Björn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Sylvia Herold, Friedrich Stölzel, Katja Sockel, Malte von Bonin, Carsten Müller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Christian Thiede, for the Study Alliance Leukemia (SAL)
Beschreibung
Zusammenfassung:Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains [CEBPAsmTAD] and 49 the C-terminal DNA-binding or basic leucine zipper region [CEBPAsmbZIP]). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.
Beschreibung:Online verfügbar 30 July 2021, Version des Artikels 6 January 2022
Gesehen am 05.10.2022
Beschreibung:Online Resource
ISSN:1528-0020
DOI:10.1182/blood.2020009680

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