Clinical Significance And Prognostic Analysis Of Gene Mutation In Adult Acute Myeloid Leukemia (non-M3)

Objective:To study the effect of gene mutation on the prognosis of primary treatment of adult patients with acute myeloid leukemia,it provides a new clinical basis for the prognosis evaluation and treatment of AML patients.Methods:Retrospective analysis of the clinical data of the initial treatment of patients who were diagnosed as adult AML in Handan Central Hospital from March 2018 to March 2022.A total of 102 patients were screened by the inclusion and exclusion criteria.To analyze the mutations between different ages,genders,chromosomal karyotypes and FAB groups of AML patients,and the mutation frequency is≥10%and the genes DNMT3A,NRAS,TET2,CSF3R,GATA2 and age,sex,chromosomal karyotype,FAB type for correlation analysis.The optimal truncation values of bone marrow primitive cells,WBC,HB and PLT counts are selected by ROC curve analysis.The correlation between gene mutations and WBC,Hb,PLT and bone marrow primitive cell counts was analyzed.Univariate Kaplan-Meier survival curve analysis was used to study the clinical baseline data and the influence of the above gene mutations on OS and PFS,and the variables of P<0.05 in univariate analysis were included in the multivariate Cox regression analysis.Results:1.The gene mutation frequency of newly diagnosed AML patients with≥10%from high to low was DNMT3A(19.6%),TET2(17.6%),FLT3-ITD(17.6%),NPM1(15.7%),NRAS(11.8%),GATA2(10.8%),CSF3R(10.8%).The mutation of DNMT3A in patients aged<60 years and≥60 years were 6/76(7.9%)vs14/26(53.8%),X~2=25.950,P=0.000.There was no significant difference in NRAS,TET2,GATA2 and CSF3R between different ages(P≥0.05).There was no significant difference in DNMT3 A,NRAS,TET2,GATA2 and CSF3R between different genders,karyotypes and FAB types(P≥0.05).2.The optimal cut-off value of bone marrow blast cells was 60%(AUC=0.666,95%CI:0.561-0.772,sensitivity 69.2%,specificity 61.9%,Youden index:0.311).The optimal cutoff value of WBC was 40×10~9/L(AUC:0.550,95%CI:0.432-0.668,sensitivity:28.2%,specificity:85.7%,Youden index:0.139).The optimal cut-off value of HB was 70g/L(AUC:0.572,95%CI: 0.460-0.685,sensitivity:59%,specificity:58.7%,Youden index:0.177).The optimal cutoff value of PLT was 40×10~9/L(AUC:0.547,95%CI:0.433-0.661,sensitivity:61.5%,specificity:54%,Youden index:0.155).There was no significant difference in DNMT3 A,NRAS,TET2,GATA2and CSF3 R between different WBC,Hb,PLT and bone marrow blast cell groups(P≥0.05).3.The average OS and PFS of AML patients with 0,1-2and≥3 gene mutations were statistically significant(P<0.05).4.Univariate Kaplan-Meier analysis:WBC≥40×10~9/L,Hb<70g/L,PLT≤40×10~9/L,bone marrow blast cell count≥60%,DNMT3A,gene mutation number≥3 may be poor prognostic factors affecting PFS.Age≥60 years old, WBC≥40×10~9/L,Hb<70g/L,PLT≤40×10~9/L,bone marrow blast count≥60%,DNMT3A,TET2,gene mutation number≥3may be adverse prognostic factors affecting OS in patients.5.Multivariate Cox regression analysis:WBC≥40×10~9/L,PLT≤40×10~9/L,bone marrow blast cell count≥60%,DNMT3 A were independent poor prognostic factors affecting PFS;w BC≥40×10~9/L,PLT≤40×10~9/L,bone marrow blast count≥60%,and the number of gene mutations≥3were independent adverse prognostic factors for OS.Conclusion:1.The most common gene mutation frequency in newly diagnosed AML patients was DNMT3 A,followed by TET2.2.DNMT3A mutation is more common in elderly AML patients.3.The number of mutations≥3 may be an adverse prognostic factor affecting PFS.4.TET2 gene mutation may be a poor prognostic factor for OS.5.WBC≥40×10~9/L,PLT≤40×10~9/L,bone marrow blast count≥60%and DNMT3 A were independent poor prognostic factors affecting PFS.6.WBC≥40×10~9/L,PLT≤40×10~9/L,bone marrow blast count≥60%,and number of gene mutations≥3 were independent poor prognostic factors affecting OS.