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

2022; Elsevier BV; Volume: 141; Issue: 15 Linguagem: Inglês

10.1182/blood.2022018108

1528-0020

Jad Othman, Manja Meggendorfer, Enrico Tiacci, Christian Thiede, Richard F. Schlenk, Richard Dillon, Sebastian Stasik, Alessandra Venanzi, Sarah Bertoli, Éric Delabesse, Pierre‐Yves Dumas, Arnaud Pigneux, Audrey Bidet, Amanda Gilkes, Ian Thomas, Maria Teresa Voso, Alessandro Rambaldi, Lorenzo Brunetti, Vincenzo Maria Perriello, Vibeke Andresen, Bjørn Tore Gjertsen, Maria Paola Martelli, Christian Récher, Christoph Röllig, Martin Bornhäuser, Hubert Serve, Carsten Müller‐Tidow, Claudia D. Baldus, T. Haferlach, Nigel H. Russell, Brunangelo Falini,

Myeloproliferative Neoplasms: Diagnosis and Treatment

NPM 1-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.