Molecular Features And Chinical Relevance Of Genetic Mutations In Pediatric Acute Myeloid Leukemia

Purpose: To characterize mutational features and prevalence of common AML genes and their impacts on prognosis of childhood acute myeloid leukemia.Method: A total of 217 pediatric AML cases were enrolled in the study, and PCR and sequencing analysis was perform to study molecular features, frequencies of WT1、IDH1/2、DNMT3A、NRAS、KRAS、FLT3、KIT、CEBPA 、NPM1. The genetic data was correlated with clinical characteristics and prognosis. We also analyzed TET rs2454206 and its relation to AML outcome.Result: Our study showed that mutational rates of WT1、IDH1/2、DNMT3A、NRAS/KRAS、FLT3-ITD、KIT、CEBPA and NPM1 were 12.4%, 1.8%, 0, 14.7%, 7.2%, 5.7%, 10.0%, and 1.4%, respectively. Survival analysis demonstrated mutant WT1/IDH1 had negative impact on OS(20.0% vs. 50.0%, p=0.034) and EFS(25.0% vs. 57.1%, p=0.038). FLT3-ITD was correlated with shorter OS(25.0% vs. 52.5%, p=0.026) and EFS(33.3% vs 60.6%, p=0.053) compared to AML with wild-type FLT3. CBF-AML with a mutant KIT had adverse prognosis compared to CBF-AML wt- OS(16.7% vs. 51.6%,p=0.030). A was the major allele of the TET2 rs2454206 in our cohort. Multivariate analysis revealed that independent poor-risk factors for OS and EFS included high WBC count(OS: HR:3.706; 95%CI: 1.463-9.392; p=0.006; EFS: HR:3.217; 95% CI: 1.113-9.302; p=0.031) and WT1/IDH1mutations(OS: HR: 3.706; 95%CI: 1.463-9.392; p=0.006; EFS: HR: 3.217; 95% CI: 1.113-9.302; p=0.031). rs2454206GA/GG was found as an independent favorable prognostic factor(OS: HR: 0.175; 95% CI: 0.062-0.492; p=0.001, EFS: HR: 0.087; 95% CI: 0.023-0.332; p﹤0.001).Conclusion: WT1 and RAS are commonly mutated in childhood AML while IDH1/2 and DNMT3 A mutants are rare. A is the major allele of the TET2 rs2454206 in Chinese pediatric AML. WT1/IDH1 mutations were associated with an inferior outcome while rs2454206GA/GG was correlated with a favorable prognosis in intermediate risk AML.