| BackgroundAcute myeloid leukemia(AML)is a group of malignant hematological diseases originated from myeloid progenitor or multipotent progenitor cells.Genetic information and mutant genes are obviously heterogeneous.With the extensive application of Next-generation sequencing(NGS)technology in the field of hematological tumors,gene mutation maps have been further explored,and prognosis stratification of AML patients has been further refined,which has significant guiding significance for accurate treatment of AML patients.At present,some studies in China have found that there are obvious differences between the karyotypes of AML patients of various age groups,taking the age of 30 and 60 as the boundary.Metzeler et al.in Germany,taking the age of 40 and 60 as the boundary,have also found that the overall comparison and the two-two comparison of the number of mutant genes in adult AML patients of different age groups have statistical significance.At the same time,there are also many reports that there are age differences and ethnic differences in the gene mutation spectrum of AML patients.However,at present,there are few comprehensive reports on the types of mutant genes,the number of mutant genes,the occurrence of multi-gene mutations and the frequency of variant alleles(VAF)in AML patients of various ages in China.ObjectiveTo compare the gene mutation differences among adult AML patients of different ages,and to analyze the effects of age and mutant genes on curative effect and prognosis.MethodsThe clinical and follow-up data of 401 newly diagnosed adult AML(≥14 years old)patients(except acute promyelocytic leukemia)from May 1,2017 to December 31,2018 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.371 cases of primary AML and 30 cases of non-primary AML(25 cases of secondary AML and 5 cases of treatment-related AML).401 patients were divided into 3 groups according to age group,including 99 patients(14～40),165 patients(41～59)and 137 patients(60～84).Based on the next generation sequencing of 22 genes,the common mutation types,the number of mutant genes,the occurrence of multi-gene mutations and the differences between the frequencies of mutant alleles in AML patients of 3 age groups were compared,and the effects of age and mutant genes on the complete remission rate and prognosis were analyzed.Results1.401 adult AML patients have a male-to-female ratio of 1.25:1,a median age of 54(14-84)years,a peripheral blood white blood cell count of 13.3(0.5-420.3)×109/L,an average hemoglobin level of 77.0(33.0～143.0)g/L,a platelet count of 38.0(3.0～754.0)×/10/L,and a bone marrow primitive and immature cell ratio of 59.6(9.2～99.2)%.Gender composition,peripheral blood cell count at first visit,FAB typing and the proportion of patients with non-primary AML were compared among the three age groups,with no significant difference(P>0.05).At first visit,the number of bone marrow primitive immature cells was lower in patients over 60 years old(P=0.036),and there was no significant difference between patients under 60 years old and patients under 2 years old(P=0.795).The proportion of induced chemotherapy patients is the lowest among patients over 60 years old(P<0.001),and the difference between patients under 60 years old and those under 2 years old is also statistically significant(P=0.002).2.The common mutation genes in patients aged(14～40)are NRAS(19.2%),KIT(17.2%),NPM1(15.2%),CEBPA double mutation(10.1%),CEBPA single mutation(10.1%).The common mutation genes in patients(41～59)years old are:NPMl(19.4%),TET2(14.5%),NRAS(13.3%),DNMT3A(12.7%),FLT3-ITD(12.1%).The common mutant genes in patients aged(60～84)are NPM1(16.8%),FLT3-ITD(15.3%),IDH2(13.9%),DNMT3A(13.1%).3.The mutation rate of IDH2,TP53 and JAK2 was higher in patients over 60 years old(P=0.036,P=0.015,P=0.006),and there was no significant difference between the two groups under 60 years old(P=0.221,P=0.632,P=0.375);TET2 has the highest mutation rate in patients aged(41～59)(P=0.009),and the difference between adults aged under 40 and over 60 is also statistically significant(4.04%vs 8.76%,P=0.005);RUNX1 mutation rate was lower in adults under 40 years old(P=0.015),and there was no significant difference between the two groups over 40 years old(P=0.367).KIT has the highest mutation rate in adult AML patients under 40 years old(P<0.001),and the difference between the two groups over 40 years old is statistically significant(8.48%vs 2.19%,P=0.023).4.Grouping by functional group-related genes:The mutation rate of epigenetic factor-related genomes in adults under 40 years old is lower(P=0.008),and there is no statistical difference between the two groups of patients over 40 years old(P=0.794);The mutation rate of tumor suppressor related genome was higher over 60 years old(P=0.030),and there was no significant difference between the two groups of patients under 60 years old(P-0.142).5.There was no significant difference in the overall gene mutation rate among the three groups(P=0.232).Mutations with 3 or more kinds of genes were more common in patients over 60 years old,and the difference was statistically significant(P=0.042).There no significant difference between patients under 60 years old and those under 2 years old(χ2=3.187,P=0.074).6.Multigene mutation combinations with frequency over 10%:(NPM1 with DNMT3A(20%)in 7 cases and NRAS with KIT mutation(11.4%)in 4 cases of patients aged(14-40)years old;(41～59)years old patients included 12 cases of NPM1 with DNMT 3A(16.7%),10 cases of NPM1 with FLT 3-ITD(13.9%),and 8 cases of NPM1 with TET2(11.1%);(60～84)years old patients included 9 cases of NPM1 with DNMT3A(14.1%),9 cases of NPM1 with FLT3-ITD(14.1%),7 cases of DNMT3A with TET2(10.9%),and 7 cases of DNMT3A with IDH2(10.9%);NRAS(16 kinds),TET2(16 kinds)and RUNX1(16 kinds)are the most common mutations in AML patients.7.TET2,DNMT3A,RUNX1 and TP53 are the genotypes with VAF values close to 100%among 22 genes.There was no significant difference in VAF values of 11 kinds of genes among patients of 3 age groups(P>0.05).8.348 patients chose induction chemotherapy,and 53.4%(186/348)patients reached CRl;the complete remission rate of first induction chemotherapy for patients over 60 years old was the lowest 39.2%(38/97)in all age groups,the difference was statistically significant(χ2=11.47,P=0.003),and there was no statistical difference between the two groups of patients under 60 years old(61.6%vs 57.2%,P=0.491).9.Among non-high white AML patients with normal karyotype under 60 years old,NRAS mutation patients had a high complete remission rate of first induction chemotherapy(100%vs 44.1%,P=0.005),and the difference was statistically significant.10.Incomplete remission of the first induction chemotherapy and IDH1 mutation were independent risk factors for the prognosis of adult normal karyotype AML(P<0.0001,P=0.0042).Conclusion1.IDH2,TP53,JAK2 mutations were concentrated in patients over 60 years old,TET2 and RUNX1 mutations were concentrated in in patients over 40 years old,KIT mutations were concentrated in patients under 60 years old.2.The most common mutation combinations in patients of the three age groups was NPM1 with DNMT3A.In addition,NPM1 with FLT3-ITD mutation was more concentrated in adults over 40 years old.NRAS with KIT mutation was more concentrated in adults under 40 years old.NPM1 with TET2 mutation was most concentrated in patients aged(40-59)years old,DNMT3A with TET2,DNMT3A with IDH2 mutation,and 3 or more gene mutations were most common in patients aged over 60 years old.3.The frequency of variant alleles is independent of age.4.NRAS mutation is a favorable factor for complete remission of the first chemotherapy in AML patients with normal karyotype under 60 years old.5.Incomplete remission of the first induction chemotherapy and IDH1 mutation are independent risk factors for the prognosis of adult AML patients with normal karyotype. 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