Influence of Nucleophosmin (NPM1) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration

Tregnago C, Benetton M, Ries RE, Peplinski JH, Alonzo TA, Stirewalt D, Othus M, Duployez N, Sonneveld E, Abrahamsson J, Fogelstrand L, von Neuhoff N, Hasle H, Reinhardt D, Meshinchi S, Locatelli F, Pigazzi M. Influence of Nucleophosmin (NPM1) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration. J Clin Oncol. 2025 Mar 10;43(8):972-984. doi: 10.1200/JCO-24-01715. Epub 2024 Dec 2. PMID: 39621969; PMCID: PMC12363388.

Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc.) have been identified. Despite molecular heterogeneity, NPM1 mutations cumulatively portend a more favorable outcome, but biology and prognostic implications of different genomic subsets have not been extensively studied. In this multicentric study, we investigated the impact of NPM1 genotypes on patients’ outcomes and interrogated the underlying biology of the different subtypes.