Clinical features and prognostic significance of DNMT3A, FLT3, and NPM1 mutations in de novo acute myeloid leukemia patients

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Objective Different co‐mutation patterns are associated with varied clinical manifestations and prognosis. The purpose of this research was to explore the clinical characteristics and prognosis of individuals with AML who had DNMT3A , FLT3 , and NPM1 mutations. Materials and Methods A total of 259 newly diagnosed AML patients were investigated in this study, including 148 AML FLT3 mut DNMT3A wt , 48 AML FLT3 wt DNMT3A mut , and 63 AML FLT3 mut DNMT3A mut patients. Mutations were detected by targeted next‐generation sequencing and Sanger sequencing. In addition, we utilized the publicly available data to analyze the expression profiles of AML. Results Correlation analysis showed NPM1 mutations were positively associated with FLT3‐ITD and DNMT3A , but negatively with CEBPA and RUNX1 mutations. In the presence of both DNMT3A and FLT3 mutations, patients were associated with typical clinical manifestations such as heavy disease burden and old age. Patients with both FLT3 and DNMT3A mutations had lower complete remission rates and poorer clinical outcomes than those with FLT3 or DNMT3A mutation alone. Univariate analysis showed that age, response to treatment, DNMT3A R882 mutation, NPM1 mutation, and consolidation treatment options were associated with OS. According to multivariate analysis, only consolidation treatment options could be considered as an independent prognostic factor. In addition, the percentage of AML FLT3 mut DNMT3A mut NPM1 mut patients in our study was about 5.9%. Interestingly, the expression profile of this subgroup was significantly related to HOX family and histone H1 family, and enriched pathways associated with transcriptional misregulation. Conclusion We comprehensively evaluated the clinical and genetic characteristics, and expression profiles of AML patients with common mutations, and found that AML patients with triple mutations might be a distinct AML subtype, which should be redefined.