Incidence and Prognostic Impact of DNMT3A Mutations in Korean Normal Karyotype Acute Myeloid Leukemia Patients

Background.DNA methyltransferase 3A(DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact ofDNMT3Amutations in Korean NK AML patients.Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled.DNMT3Amutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based onin silicoanalysis results. Clinical features and prognosis were compared with respect toDNMT3Amutation status.Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs.DNMT3ANSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively.DNMT3Amutations were frequently detected inFLT3ITD mutated patients (P= 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly.Conclusions. Incidences ofDNMT3ANSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients.DNMT3Amutations are associated withFLT3ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients.