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Overlapping features of therapy-related and de novo NPM1-mutated AML

NPM1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of “therapy-related” NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared the genetics, transcriptional profile, and clinical outcomes of t-NPM1 AML, de novo NPM1-mutated AML (dn-NPM1 AML), and...

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Main Authors: Othman, Jad (Author) , Meggendorfer, Manja (Author) , Tiacci, Enrico (Author) , Thiede, Christian (Author) , Schlenk, Richard Friedrich (Author) , Dillon, Richard (Author) , Stasik, Sebastian (Author) , Venanzi, Alessandra (Author) , Bertoli, Sarah (Author) , Delabesse, Eric (Author) , Dumas, Pierre-Yves (Author) , Pigneux, Arnaud (Author) , Bidet, Audrey (Author) , Gilkes, Amanda F. (Author) , Thomas, Ian (Author) , Voso, Maria Teresa (Author) , Rambaldi, Alessandro (Author) , Brunetti, Lorenzo (Author) , Perriello, Vincenzo M. (Author) , Andresen, Vibeke (Author) , Gjertsen, Bjorn T. (Author) , Martelli, Maria Paola (Author) , Récher, Christian (Author) , Röllig, Christoph (Author) , Bornhäuser, Martin (Author) , Serve, Hubert (Author) , Müller-Tidow, Carsten (Author) , Baldus, Claudia D. (Author) , Haferlach, Tortsten (Author) , Russell, Nigel (Author) , Falini, Brunangelo (Author)
Format: Article (Journal)
Language:English
Published: April 13, 2023
In: Blood
Year: 2023, Volume: 141, Issue: 15, Pages: 1846-1857
ISSN:1528-0020
DOI:10.1182/blood.2022018108
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2022018108
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Author Notes:Jad Othman, Manja Meggendorfer, Enrico Tiacci, Christian Thiede, Richard Schlenk, Richard Dillon, Sebastian Stasik, Alessandra Venanzi, Sarah Bertoli, Eric Delabesse, Pierre-Yves Dumas, Arnaud Pigneux, Audrey Bidet, Amanda F. Gilkes, Ian Thomas, Maria Teresa Voso, Alessandro Rambaldi, Lorenzo Brunetti, Vincenzo M. Perriello, Vibeke Andresen, Bjorn T. Gjertsen, Maria Paola Martelli, Christian Récher, Christoph Röllig, Martin Bornhäuser, Hubert Serve, Carsten Müller-Tidow, Claudia D. Baldus, Tortsten Haferlach, Nigel Russell, Brunangelo Falini

MARC

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245 1 0 |a Overlapping features of therapy-related and de novo NPM1-mutated AML  |c Jad Othman, Manja Meggendorfer, Enrico Tiacci, Christian Thiede, Richard Schlenk, Richard Dillon, Sebastian Stasik, Alessandra Venanzi, Sarah Bertoli, Eric Delabesse, Pierre-Yves Dumas, Arnaud Pigneux, Audrey Bidet, Amanda F. Gilkes, Ian Thomas, Maria Teresa Voso, Alessandro Rambaldi, Lorenzo Brunetti, Vincenzo M. Perriello, Vibeke Andresen, Bjorn T. Gjertsen, Maria Paola Martelli, Christian Récher, Christoph Röllig, Martin Bornhäuser, Hubert Serve, Carsten Müller-Tidow, Claudia D. Baldus, Tortsten Haferlach, Nigel Russell, Brunangelo Falini 
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520 |a NPM1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of “therapy-related” NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared the genetics, transcriptional profile, and clinical outcomes of t-NPM1 AML, de novo NPM1-mutated AML (dn-NPM1 AML), and therapy-related AML (t-AML) with wild-type NPM1 (t-AML). Normal karyotype was more frequent in t-NPM1 AML (n = 78/96, 88%) and dn-NPM1 (n = 1986/2394, 88%) than in t-AML (n = 103/390, 28%; P < .001). DNMT3A and TET2 were mutated in 43% and 40% of t-NPM1 AML (n = 107), similar to dn-NPM1 (n = 88, 48% and 30%; P > 0.1), but more frequently than t-AML (n = 162; 14% and 10%; P < 0.001). Often mutated in t-AML, TP53 and PPM1D were wild-type in 97% and 96% of t-NPM1 AML, respectively. t-NPM1 and dn-NPM1 AML were transcriptionally similar, (including HOX genes upregulation). At 62 months of median follow-up, the 3-year overall survival (OS) for t-NPM1 AML (n = 96), dn-NPM1 AML (n = 2394), and t-AML (n = 390) were 54%, 60%, and 31%, respectively. In multivariable analysis, OS was similar for the NPM1-mutated groups (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.65-1.25; P = .45), but better in t-NPM1 AML than in t-AML (HR, 1.86; 95% CI, 1.30-2.68; P < .001). Relapse-free survival was similar between t-NPM1 and dn-NPM1 AML (HR, 1.02; 95% CI, 0.72-1.467; P = .90), but significantly higher in t-NPM1 AML versus t-AML (HR, 1.77; 95% CI, 1.19-2.64; P = .0045). t-NPM1 and dn-NPM1 AML have overlapping features, suggesting that they should be classified as a single disease entity. 
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