Accurate classification and risk prediction are critical for therapeutic decision-making in patients with acute myeloid leukaemia (AML). Myelodysplasia-related (MR) gene mutations are classified as adverse genetic factors by the European LeukaemiaNet-2022 guidelines. However, their prognostic value in de novo AML remains controversial. This study retrospectively analysed 188 patients with de novo AML-MR, stratifying them into four subgroups based on dynamic measurable residual disease (MRD) after induction, one or two courses of consolidation chemotherapy. The median follow-up was 36.8 months (4.6-73.7). Patients with persistent or recurrent MRD positivity after the second consolidation had the poorest 3-year relapse-free survival (RFS), overall survival (OS) and cumulative incidence of relapse compared to the other groups (p <
0.001). Multivariable analysis identified this high-risk group as an independent risk factor for both RFS and OS. We observed significant heterogeneity of OS benefit from allogeneic stem cell transplantation (allo-SCT) by MRD-risk groups, with substantial OS advantage for patients in subgroup D (3-year OS: allo-SCT 70.0% vs. 18.2% without, p <
0.001) but no benefit for others (p = 0.047 for interaction). This study underscores the importance of dynamic MRD in refining risk stratification and identifying de novo AML patients with MR mutations who would benefit from allo-SCT during the first complete remission.