Abstract

To investigate the carrier rate and clinical characteristics of epigenetic modification gene mutations (EMMs) among patients with acute myeloid leukemia (AML). One hundred seventy two patients who were initially diagnosed with AML at the First People's Hospital of Lianyungang from May 2011 to February 2021 were selected as the study subjects. Next-generation sequencing was carried out to detect variants of 42 myeloid genes among these patients. Clinical and molecular characteristics of patients with EMMs and the effect of demethylation drugs (HMAs) on their survival were analyzed. Among the 172 AML patients, 71 (41.28%) were found to harbor the EMMs, and carrier rates were TET2 (14.53%, 25/172), DNMT3A (11.63%, 20/172), ASXL1 (9.30%, 16/172), IDH2 (9.30%, 16/172), IDH1 (8.14%, 14/172), EZH2 (0.58%, 1/172). Patients with EMMs (+) had lower peripheral hemoglobin compared with those with EMMs(-) (72 g/L vs. 88 g/L, Z = -1.985, P = 0.041). The proportion of EMMs(+) among elderly AML patients was significantly higher than that of young AML patients[71.11% (32/45) vs. 30.70% (39/127), χ² = 22.38, P < 0.001]. EMMs(+) were significantly correlated with NPM1 gene variants (r = 0.413, P < 0.001), while negatively correlated with CEPBA double variants (r = -0.219, P < 0.05). Compared with conventional chemotherapy regimens, HMAs-containing chemotherapy regimens have improved the median progression-free survival (PFS) and median overall survival (OS) among intermediate-risk AML patients with EMMs(+) (PFS: 11.5 months vs. 25.5 months, P < 0.05; 12.5 months vs. 27 months, P < 0.05). Similarly, Compared with conventional chemotherapy regimens, chemotherapy with HMAs had increased median PFS and median OS in elderly AML patients with EMMs(+) (4 months vs. 18.5 months, P < 0.05; 7 months vs. 23.5 months, P < 0.05). Patients with AML have a high rate of EMMs carriage, and HMAs-containing chemotherapy regimens can prolong the survival of elderly patients with AML with poor prognosis, which may provide a reference for individualized treatment.

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