Abstract:Objective:To investigate the different patterns of additional gene mutation accompanied withCEBPAbiallelic 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 withCEBPAbiallelic and monoallelic mutations were analyzed by Chi-square or Fisher's exact test.Results:In the 152 patients,CEBPAbiallelic 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 carriedCEBPAmonoallelic mutations (4 cases, 30.77%) was higher than that of the patients withCEBPAbiallelic mutations (3 cases, 6.98%) (P=0.043). NoNPM1gene mutation was found in patients withCEBPAbiallelic mutated, while near half of the patients (6 cases, 46.15%) hadCEBPAmonoallelic mutations accompanied withNPM1mutation.CEBPAmonoallelic mutated patients were more involved in genes of DNA methylation group (DNMT3A,TET2,IDH1,IDH2) than those withCEBPAbiallelic mutation (7 cases, 53.85%vs10 cases, 23.26%,P=0.046). Meanwhile, more high-risk genes (DNMT3A,FLT3-ITD,TP53) co-mutated were found in patients withCEBPAmonoallelic mutations than those withCEBPAbiallelic mutations.Conclusions:Compared with patients withCEBPAbiallelic mutation, theCEBPAmonoallelic 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.

Key words:Acute myeloid leukemia, CEBPA ,Additional gene mutations,Mechanism