Prognostic impact of CEBPA mutational subgroups in adult AML

Georgi, Julia-Annabell, Stasik, Sebastian, Kramer, Michael, Meggendorfer, Manja, Röllig, Christoph, Haferlach, Torsten, Valk, Peter, Linch, David, Herold, Tobias, Duployez, Nicolas, Taube, Franziska, Middeke, Jan Moritz, Platzbecker, Uwe, Serve, Hubert, Baldus, Claudia D., Muller-Tidow, Carsten, Haferlach, Claudia, Koch, Sarah, Berdel, Wolfgang E., Woermann, Bernhard J., Krug, Utz, Braess, Jan, Hiddemann, Wolfgang, Spiekermann, Karsten, Boertjes, Emma L., Hills, Robert K., Burnett, Alan, Ehninger, Gerhard, Metzeler, Klaus, Rothenberg-Thurley, Maja, Dufour, Annika, Dombret, Hervé, Pautas, Cecile, Preudhomme, Claude, Fenwarth, Laurene, Bornhäuser, Martin, Gale, Rosemary and Thiede, Christian 2024. Prognostic impact of CEBPA mutational subgroups in adult AML. Leukemia 38 (2) , pp. 281-290. 10.1038/s41375-024-02140-x

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Abstract

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0887-6924
Date of First Compliant Deposit:	6 February 2024
Date of Acceptance:	5 January 2024
Last Modified:	06 Feb 2024 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/166150

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