Prognostic impact of CEBPA mutational subgroups in adult AML
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...
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
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16 January 2024
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| In: |
Leukemia
Year: 2024, Jahrgang: 38, Heft: 2, Pages: 281-290 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-024-02140-x |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-024-02140-x Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-024-02140-x 
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| Verfasserangaben: | 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. Woermann, Utz 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 and Christian Thiede |
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| 245 | 1 | 0 | |a Prognostic impact of CEBPA mutational subgroups in adult AML |c 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. Woermann, Utz 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 and Christian Thiede |
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| 520 | |a 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). | ||
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