Effects of different gene mutations on the prognosis of acute myeloid leukemia
Objective:To investigate the gene mutation landscape and its relationship with prognosis in acute myeloid leukemia(AML)patients.Methods:Retrospective analysis of clinical data from AML patients newly diagnosed between January 2018 and December 2021 in the Department of Hematology,the Third Affiliated Hospital of Sun Yat-sen University.Targeted deep sequencing(NGS 175-Panel)identified gene mutations.Mutation landscape,co-occurrence,mutual exclusivity,and associations with clinical features were analyzed.Kaplan-Meier and Cox proportional-hazards model assessed gene mutation-related prognosis,including overall survival(OS)and event-free survival(EFS).Results:Among 140 AML cases,433 mutations occurred.Top 5 mutated genes were FLT3,CEBPA,NPM1,WT1,and IDH2.WT1,CEBPA,NPM1,and DNMT3A mutation frequencies were significantly higher than those in Western populations.Significant co-occurrence or mutual exclusivity existing between 22 gene pairs,and various gene mutations correlated with clinical features were discovered(all P<0.05).FLT3-ITD(OS:P=0.047,EFS:P=0.097),NRAS(OS:P=0.003,EFS:P=0.300),and WT1(OS:P=0.110,EFS:P=0.004)were associated with poorer OS or EFS.FLT3-ITD positive with WT1 mutations had significantly worse OS and EFS than double-negative or single-positive AML patients(OS:P<0.001,EFS:P=0.005).Meanwhile,FLT3-ITD insertion sites were explored for correlations with clinical characteristics and prognosis,the results showed a significantly poorer OS when FLT3-ITD inserted solely in the juxtamembrane domain(JMDsole),compared to insertions between the juxtamembrane domain and tyrosine kinase domain 1(JMD/TKD1)(P=0.007).Conclusions:AML genetic mutation landscape differ across populations.NRAS,WT1 mutations,and FLT3-ITD and WT1 co-mutations suggest an unfavorable prognosis.
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