To explore the mutational characteristics in 125 elderly and young patients with acute myeloid leukemia with DNMT3A mutation.

From November 2014 to October 2020, 230 patients with de novo AML who were ≥60 years old and diagnosed at Changzhou Second People's Hospital, Wuxi Second People's Hospital, and Wuxi Third People's Hospital were selected. Sixty-five elderly AML patients with DNMT3A mutation were screened out, and tumor typing was performed by morphological typing, immunoassay (flow cytometry), cell biology, and molecular biology (MICM) typing. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and Sanger sequencing.

All the 65 elderly cases had co-mutations at diagnosis, and there was an average number of mutations of 4.8 (range, 1-11) per case in addition to DNMT3A mutation. The most common concomitant mutation was NPM1 (44.62%, 29/65), followed by FLT3-ITD (33.33%, 20/65), TET2 (23.07%, 15/65), RUNX1 (15.38%, 10/65), IDH1 (15.38%, 10/65), IDH2 (13.85%, 9/65), and PTPN11 (12.31%, 8/65). Compared with the 60 young AML patients with DNMT3A, both NPM1 (44.62% vs. 68.33%, P=0.008) and KIT (0 vs 10.0%, P=0.009) mutations were found less frequently in 65 elderly patients. However, elderly AML patients had a signi?cantly higher incidence of TET2 (23.07% vs 1.67%, P=0.0001) and RUNX1 (15.38% vs 3.33%, P=0.022) mutations than oung AML patient, and all ETV6 and SRSF2 mutations were found in the elderly group (P=0.051 and 0.092, respectively). Functionally, 65 elderly patients had a higher incidence of epigenetic regulatory gene mutations, and the difference was significant between the two groups (47.69% vs 23.33%, P=0.005). Compared with patients with a wild-type locus, patients with FLT3-ITD mutations exhibited higher peripheral WBC levels (P=0.003) and lower induced initial complete remission (CR) (P=0.008). Elderly patients with PTPN11 gene mutation had higher platelet levels (P=0.048). Elderly patients with NPM1, TET2, IDH1/2, and RUNX1 mutations had no statistically significant difference in CR rates or peripheral blood cell levels. The overall induced initial remission rate was significantly lower in the elderly patients than in the young patients (34.55% vs 73.08%, P=0.0001). Elderly AML patients with FLT3-ITD or NPM1 mutation had a lower CR rate than young adults (P=0.005, 0.001).

AML elderly patients with DNMT3A mutation commonly show additional mutations. The mutational landscape is different from that of young patients. Some coexisting gene mutations have a certain impact on the clinical characteristics and CR rate of AML elderly patients.