The impact of DNMT3A mutation on survival of AML patients receiving allotransplant in first remission depends on the karyotype and co-occurring mutations

Authors	IMAN Abou Dalle GALIMARD Jacques-Emmanuel POIRE Xavier SANZ Jaime HUYNH Anne KROGER Nicolaus WAGNER-DROUET Eva Maria BURNS David EDER Matthias LIOURE Bruno WU Depei MAYER Jiří CARLSON Kristina STELLJES Matthias COLLIN Matthew ALJURF Mahmoud NAGLER Arnon ESTEVE Jordi CICERI Fabio BAZARBACHI Ali MOHTY Mohamad
Year of publication	2026
Type	Peer-reviewed scientific article
Magazine / Source	Bone Marrow Transplantation
MU Faculty or unit	Faculty of Medicine
Citation
web	https://www.nature.com/articles/s41409-025-02765-1
Doi	https://doi.org/10.1038/s41409-025-02765-1
Keywords	acute myeloid leukemia; DNMT3A mutation; allogeneic transplantation; first remission; co-occurring mutations
Description	Mutations in the DNMT3A gene are not yet classified as a distinct prognostic group in the latest European Leukemia Net (ELN) 2022 genetic risk classification of AML. We analyzed 1888 adult AML patients with ELN 2022 intermediate- or poor-risk cytogenetics who received their first allo-transplant in first complete remission between 2015 and 2022. Among patients with cytogenetically normal AML, the triple-positive mutation group (DNMT3A, NPM1, and FLT3-ITD) was the most frequent (n = 340, 29%), while DNMT3A co-occurrence with either FLT3 or NPM1 mutations alone was less common (4% and 9%, respectively). Patients with DNMT3A mutations were less likely to have a secondary AML (14% versus 24%, p < 0.001). DNMT3A mutations negatively affected post-transplant leukemia-free survival (LFS) in patients with normal karyotype and NPM1 mutation without FLT3-ITD (2-year LFS: 70% versus 90%, hazard ratio [HR]: 3.3, p = 0.006), and increased relapse incidence (RI) in FLT3-ITD and wild-type NPM1 subgroup (2-year RI: 30% versus 18%, HR: 2.32, p = 0.03). Notably, patients with normal karyotype and triple-positive mutation exhibited excellent 2-year LFS and OS (61% and 70%), indicating that allo-transplant overcomes the dismal outcome of this group. The impact of DNMT3A mutations on post-transplant outcomes in AML patients in first remission varies based on karyotype and co-mutations.