| Objective:While young and middle-aged patients with acute myeloid leukemia(AML)can be accurately stratified,the significant heterogeneity of biological characteristics among elderly AML patients has made stratification and achieving positive clinical outcomes difficult.In this paper,we comprehensively evaluate the biological and clinical characteristics of elderly AML patients by exploring the relationship between gene mutations and factors such as FAB classification,immunophenotype,karyotype,and other biological and clinical characteristics.Our aim is to provide some references to aid in the prognosis stratification and clinical treatment of this special population.Methods:Between April 2015 and March 2021,we enrolled 90 newly diagnosed elderly acute myeloid leukemia(AML)patients aged 60 years or above,who were detected with gene mutations by next-generation sequencing(NGS)in our medical center.We collected information on their gene mutations,FAB classification,chromosome karyotype,immunophenotype,chemotherapy scheme,remission status after treatment,follow-up survival status,and other biological and clinical features.We then explored the correlation between gene mutations and these features,as well as the impact of such correlations on prognosis.Results:(1)Frequency and distribution:Out of the 90 patients,a total of 29 gene mutations were identified in 82 patients.Among them,17 gene mutations were present in more than 5%of the patients.(2)Association of gene mutations with biological/clinical features of elderly AML patients:DNMT3A,BCOR,U2AF1,and BCORL1 mutations were found to be unevenly distributed among different FAB classifications(=0.007,0.048,0.039,0.014).Additionally,DNMT3A,IDH2,NPM1,FLT3-ITD,ASXL1,IDH1,SRSF2,BCOR,NRAS,RUNX1,U2AF1,and WT1 mutations showed different distribution in patients depending on whether an immunophenotype was expressed or not(<0.05).Notably,NPM1 and FLT3-ITD mutations had a higher frequency in patients with normal chromosome karyotype than those with abnormal karyotype(<0.001,=0.005).(3)The impact of single gene mutations on prognosis was investigated in a cohort of 90elderly patients with acute myeloid leukemia(AML).Patients with mutations in DNMT3A or NRAS had significantly lower complete remission(CR)rates than those with wild type genes(=0.015,0.025)in the total cohort.Similarly,in the subgroup of63 patients in the favorable-risk or intermediate-risk group,those with DNMT3A or NRAS mutations had significantly lower CR rates than those without the mutations(=0.023,0.019).DNMT3A mutations were associated with significantly shorter overall survival(OS)in both the total cohort and the favorable or intermediate-risk group(one-year OS rates:21.7%vs 47.8%,=0.029 and 25%vs 55.3%,=0.036,respectively).Patients with TP53 mutations had a trend of inferior OS(one-year OS rates:10%vs 45%,=0.043),and those with mutant U2AF1 had an unfavorable OS(one-year OS rates:0 vs 44.6%,=0.039).Univariate survival analysis showed that DNMT3A,TP53,NRAS,and U2AF1 mutations predicted shorter OS(=0.013,=0.021,=0.002,<0.001).Additionally,NPM1 mutations predicted longer RFS(=0.043),while mutations in RUNX1,U2AF1,WT1,and FLT3-TKD predicted shorter RFS(=0.02,<0.001,=0.015,=0.012).(4)Several pairs of gene mutations have been found to coexist in patients with AML,and statistical analysis has revealed significant relationships among some of them.These pairs include TET2 and RUNX1 mutation(=0.047),NPM1 and IDH2 mutation(=0.039),NPM1 and FLT-ITD mutation(=0.006),CEBPA and WT1 mutation(=0.009),SRSF2 and ASXL1 mutation(=0.025),SRSF2 and IDH1 mutation(=0.025),FLT3-TKD and DNMT3A mutation(=0.014),FLT3-TKD and RUNX1 mutation(=0.014).Additionally,the co-occurrence of ASXL1 and U2AF1 mutations was found to predict a lower one-year overall survival rate(=0.047)and shorter OS(=0.003).(5)The association between gene mutations and MIC classification has a significant impact on prognosis.In patients with TET2 mutation,the complete remission(CR)rate was distributed differently among different FAB classifications(M2:66.7%,M4:0,M5:12.5%;=0.043).When TET2 was mutant,the CR rates were significantly different between patients with CD123+vs CD123-(20%vs 64.3%,=0.047),CD11b+vs CD11b-(0 vs 57.9%,=0.041),and CD34+vs CD34-(66.7%vs 11.1%,=0.013).Similarly,in patients with IDH2 mutation,the CR rates were significantly different between patients with CD34+vs CD34-(75%vs 20%,=0.01).In patients with ASXL1 mutation,CD38+predicted shorter overall survival(OS)than CD38-(one-year OS:0 vs 66.7%,=0.038).When SRSF2 was mutant in patients,CD123+predicted longer OS than CD123-(one-year OS rates:80%vs 12.5%,=0.032).(6)A multivariate analysis was conducted to determine the survival of elderly patients with acute myeloid leukemia(AML).For overall survival(OS),TP53 mutation,platelet count less than 51×10~9/L,hyperleukocytic leukemia,the presence of four or more gene mutations,and failure to achieve complete remission(CR)after induction chemotherapy were identified as independent risk factors.For relapse-free survival(RFS),the presence of CD34+cells was identified as an independent risk factor.Conclusions:(1)The incidence of gene mutations was found to be high in elderly patients with acute myeloid leukemia(AML),with a wide variety of mutations identified.(2)In elderly patients with acute myeloid leukemia(AML),single gene mutations in DNMT3A or NRAS were found to predict lower complete remission(CR)rates following induction chemotherapy.Additionally,single gene mutations in DNMT3A,TP53,NRAS,and U2AF1,as well as co-mutations in ASXL1 and U2AF1,were associated with shorter OS.Conversely,NPM1 mutation was associated with longer RFS.Single gene mutations in RUNX1,U2AF1,WT1,and FLT3-TKD were found to be associated with shorter RFS.Furthermore,TP53 mutation and the presence of four or more gene mutations were identified as independent risk factors for OS.(3)Correlations have been found between gene mutations and the patient’s morphological,immunophenotypic,and chromosomal characteristics in elderly patients with acute myeloid leukemia(AML),with some of these correlations affecting the patient’s prognosis.For example,in patients with TET2 mutations,CD123+,CD11b+,and CD34-expression were associated with a lower complete remission(CR)rate.Additionally,patients with ASXL1+CD38+expression had a shorter overall survival(OS)compared to those with ASXL1+CD38-expression.Conversely,patients with SRSF2+CD123+expression had longer OS compared to those with SRSF2+CD123-expression.(4)Detecting gene mutations in elderly patients with acute myeloid leukemia(AML)at the time of their initial diagnosis and conducting correlation analysis with other biological/clinical characteristics can be helpful in accurately guiding prognosis stratification and clinical treatment for these patients. |
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