Objective: To investigate the different patterns of additional gene mutation accompanied with CEBPA biallelic or monoallelic mutations in patients with acute myeloid leukemia, which might be associated with different prognosis of these two kinds of mutation subtypes. Methods: A total of 152 newly diagnosed acute myeloid leukemia patients with normal karyotype were enrolled. The mutations in hot spot regions of 25 AML driver genes were screened using next-generation sequencing strategy and the discovered mutation sites were confirmed by Sanger sequencing. The difference in additional gene mutation patterns accompanied with CEBPA biallelic and monoallelic mutations were analyzed by Chi-square or Fisher's exact test. Results: In the 152 patients, CEBPA biallelic mutations were identified in 43(28.29%) cases and monoallelic mutations in 13(8.55%) cases. The ratio of more than 3 additional gene mutations in patients carried CEBPA monoallelic mutations (4 cases, 30.77%) was higher than that of the patients with CEBPA biallelic mutations (3 cases, 6.98%) (P=0.043). No NPM1 gene mutation was found in patients with CEBPA biallelic mutated, while near half of the patients (6 cases, 46.15%) had CEBPA monoallelic mutations accompanied with NPM1 mutation. CEBPA monoallelic mutated patients were more involved in genes of DNA methylation group (DNMT3A, TET2, IDH1, IDH2) than those with CEBPA biallelic mutation (7 cases, 53.85% vs 10 cases, 23.26%, P=0.046). Meanwhile, more high-risk genes (DNMT3A, FLT3-ITD, TP53) co-mutated were found in patients with CEBPA monoallelic mutations than those with CEBPA biallelic mutations. Conclusions: Compared with patients with CEBPA biallelic mutation, the CEBPA monoallelic mutation cohort have more additional gene mutations associated with adverse prognosis, and the different gene mutation patterns may lead to different prognosis. However, more large-scale investigations are needed to verify their clinical significance.
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