Prognostic impact of CEBPA mutational subgroups in adult AML

Julia Annabell Georgi, Sebastian Stasik, Michael Kramer, Manja Meggendorfer, Christoph Röllig, Torsten Haferlach, Peter Valk, David Linch, Tobias Herold, Nicolas Duployez, Franziska Taube, Jan Moritz Middeke, Uwe Platzbecker, Hubert Serve, Claudia D. Baldus, Carsten Muller-Tidow, Claudia Haferlach, Sarah Koch, Wolfgang E. Berdel, Bernhard J. WoermannUtz Krug, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann, Emma L. Boertjes, Robert K. Hills, Alan Burnett, Gerhard Ehninger, Klaus Metzeler, Maja Rothenberg-Thurley, Annika Dufour, Hervé Dombret, Cecile Pautas, Claude Preudhomme, Laurene Fenwarth, Martin Bornhäuser, Rosemary Gale, Christian Thiede*

*Corresponding author for this work

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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 (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel 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 bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel 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 bZIP ms). (Figure presented.)

Original languageEnglish
Pages (from-to)281-290
Number of pages10
Issue number2
Early online date16 Jan 2024
Publication statusPublished - Feb 2024

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