| Objective:To understand the characteristics of genetic mutations in different age groups of elderly patients with acute myeloid leukemia and the correlation between different karyotypes and gene mutations.Explore the effects of common gene mutations on clinical characteristics,CR rate,and prognosis.Methods:The clinical data,cytogenetics and molecular biology data of 102 patients with newly diagnosed AML(?60 years old,non-APL)in the Department of Hematology,First Hospital of Jilin University from December 2015 to July 2018 were retrospectively analyzed.Calculate the characteristics of gene mutations in different age groups.Combine chromosomes to explore the effects of gene mutations on prognosis stratification.To explore the differences in the proportions of WBC,HGB,PLT,peripheral blood and bone marrow blasts in patients with different gene mutations.To explore the effect of gene mutation on CR rate and overall survival.Results:1.Among the 102 patients,55(53.92%)were male and 47(46.08%)were female,with a median age of 65(62-68).At the time of initial diagnosis,the median peripheral blood leukocyte count was 12.77(2.31~52.42)×10~9/L,hemoglobin 80.00(62.75~96.25)g/L,platelet 54.00(25.75~95.00)×10~9/L.The proportion of median bone marrow blast cells was 66.75%,and the proportion of peripheral blood blast cells was 34.00%.2.Among the 102 patients,89 patients underwent karyotype analysis,81 of whom were found to be able to analyze the segregation phase.The successful detection rate was 90.01%.There were 58 normal karyotypes(71.60%).Abnormal karyotype in 23 cases(28.40%),including t(8;21)(q22;q22)7 cases(30.43%),inv(16)(p13q22)1 case(4.35%),complex karyotype 2 cases(8.70)%),1 case of-7karyotype(4.35%),12 cases of other chromosomal abnormalities(52.17%).According to cytogenetics,there were 3 cases of high-risk karyotype(complex karyotype and-7),70 cases of moderate-risk karyotype(normal karyotype and other karyotypes),and 8 cases of low-risk karyotype(t(8;21)and inv(16)).The proportion of medium-risk karyotypes was the highest(86.42%).3.Molecular biological tests were performed in 102 patients,and 46 mutant genes were detected.The genes with mutation rate above 10%were DNMT3A(38.24%),NPM1(29.41%),FLT3-ITD(21.57%),and TET2(21.57%),RUNX1(16.67%),NRAS(15.69%),IDH2(13.73%),SRSF2(13.73%),FLT3-TKD(12.75%),CEBPA(11.76%,double mutation 5 cases,single mutation 7 cases)),BCOR(10.78%).Moreover,the mutation rate of DNMT3A,TET2 and FLT3-ITD increased with age over 60 years old,and SRSF2 increased with age over 65 years old.Combined molecular biology,according to the Chinese adult acute myeloid leukemia guidelines for Chinese diagnosis and treatment(2017 edition)standard stratification,55 patients(67.90%)in the high-risk group,15 patients(18.52%)in the intermediate-risk group,and 11 patients in the low-risk group(13.58%)).The proportion of high-risk groups has increased significantly.After grouping according to age,the proportion of high-risk groups gradually increased with age.4.Of the 8 well-preferred karyotypes,4 had KIT mutations.Two complex karyotypes were associated with TP53 mutations.In 58 normal karyotype patients,the mutant gene was detected,and the highest proportion of DNMT3A mutation was48.28%(28 cases).5.DNMT3A,NPM1,and FLT3-ITD are interconnected with 32,25,and 19genes,respectively,and the three are most commonly associated with each other.TET2 has 26 genes interconnected,the most common being DNMT3A,NPM1,FLT3-ITD,NRAS,etc.6.The number of white blood cells,the proportion of bone marrow blast cells and the percentage of peripheral blood blast cells in FLT3-ITD mutation patients were higher.The peripheral blood leukocyte counts of patients with NPM1 mutation and TET2 mutation were higher,the hemoglobin of patients with NRAS mutation was lower,and the number of white blood cells of patients with IDH1/2 mutation was lower.The FLT3-TKD mutation has a higher proportion of bone marrow blast cells.The differences were statistically significant(P<0.05).7.Of the 102 patients,76 were treated,and 63 patients were evaluated.37patients were treated with CR for 1 to 2 courses,and the CR rate was 58.73%.The CR rate of patients with RUNX1 mutation and BCOR/BCORL1 mutation was lower than that of patients without this mutation,and the difference was statistically significant(P<0.05).8.Sixty-three patients with evaluable patients were included in the survival analysis.The median survival time was 8 months.Univariate analysis showed that NPM1 mutation may be associated with better prognosis.RUNX1 mutation may be associated with poor prognosis.Conclusions:1.There are many gene mutations in elderly AML patients,and the frequency of various gene mutations is different from that of young patients.The most common mutation gene in this group is DNMT3A,followed by NPM1,FLT3-ITD,TET2 and so on.And the incidences of DNMT3A,TET2,FLT3-ITD mutations increase with age over 60 years old.The incidence of SRSF2 increases with age over 65 years old.2.Combining gene mutations and chromosomes can make prognosis stratification more precise.Combining gene stratification can make the stratification of highly heterogeneous medium-risk karyotypes more detailed.The proportion of patients with high-risk prognosis in elderly AML increases with age.3.Different gene mutations have different effects on clinical characteristics,CR rate and overall survival of elderly patients with AML.In this group of patients,FLT3-ITD mutation patients have a higher proportion of white blood cells,bone marrow and peripheral blood blast cells.Patients with NPM1 mutation and TET2mutation had higher white blood cell counts,and the number of white blood cells in patients with IDH1/2 mutation was lower.The proportion of bone marrow blast cells in FLT3-TKD mutation patients was higher.FLT3-ITD,DNMT3A,and TET2mutations had no significant effect on CR rate and overall survival.Patients with BCOR mutations had lower CR rates.NPM1 mutations may be associated with good prognosis.RUNX1 mutations may be associated with low CR rates and poor prognosis. |
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