DNMT3Amutations in acute myeloid leukemia: stability during disease evolution and clinical implications

DNMT3Amutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 patients with de novo AML, DNMT3Amutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3Amutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3internal tandem duplication, and NPM1, PTPN11, and IDH2mutations, but were negatively associated with CEBPAmutations. Multivariate analysis demonstrated that the DNMT3Amutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3Amutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P< .001). Sequential study of 138 patients during the clinical course showed that DNMT3Amutations were stable during AML evolution. In conclusion, DNMT3Amutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3Amutation may be a potential biomarker for monitoring of minimal residual disease.