The Detection And Clinical Significance Of The Genes In Acute Myeloid Leukemia(no-M3)

Objective:To investigate the prognostic gene expression and clinical characteristics in de novo acute myeloid leukemia who had been detect 31 kinds of fusion genes and four kinds mutation genes.Meanwhile observing the efficiency and prognosis,providing theory evidence for individual diagnose and treatment.Methods:The retrospective methodology includes in this study.175 newly diagnosed AML patients(no-M3)were all from the hematology department of the first affiliated hospital of Nanchang University during August 2013 to December 2016.All of them were detected the 31 kinds of fusion genes,and among of them,132 cases detected four kinds mutation genes.All of them were diagnosed by Morphology,Immunology,Cytogenetics and Molecular Biology include the transformed from MDS.Clinical characteristics and prognosis had been had been comparatively and statistically analyzed.Results:1)Among the 175 AML patients,64 patients with one or two fusion genes expression,the positive rate was 36.57%.29 cases(16.57%)with AML1/ETO expression,13 cases(7.42%)with MLL fusion gene expression,9 cases(4.57%)with HOX11expression,6 cases(3.43%)with CBF?/MYH11 expression,2cases(1.14%)with DEK/CAN expression,12cases(6.86%)with EVI1 expression,other genes were not fund;2)59 cases with gene mutation were found in the 132 AML patients,the mutation rate was 44.69%(59/132),and there were 10 patients with double mutation;four kinds of mutation gene can been detected,21 cases NPM1 mutation?20cases FLT3/ITD mutation?20 cases CEBPA mutation?8cases C-kit/D816Y mutation.3)According to FAB classification,gene abnormality were more observed in FAB subgroup AML-M2(35.93%)?AML-M5(42.18%);4)AML1/ETO expression was more observed in FAB subgroup M2;the average age was 32 years old,which were younger than AML1/ETO~-patients(P=0.012,<0.05).What's more,AML1/ETO~+offen correlation with C-kit/D816(P=0.001,<0.05)and have significantly high CR rate(P=0.023,<0.05).However,the CR rate was of short duration(P=0.000,<0.05),the relapse rate 33.33%(P=0.590).Among the EVI1~+patients,MLL~+fusion gene was often followed expression(P=0.001);When cut off in 50 years old,HOX11 expression had the tendency in old age patients(p=0.003,<0.05)CBF?/MYH11~+was rarely seen in AML.5)FLT3/ITD~+mutation had high peripheral WBC count,61.51×10~9g/l(P=0.005,<0.05)and was easily occuring with NPM1 mutation(p<0.05).And there had no difference in CR rate OS,but the survival time of FLT3/ITD~+AML was short than FLT3/ITD~-AML and were relative to poor prognosis;the mutation rate of NPM1 was17.35%,and often combined with FLT3/ITD~+mutation(P=0.028,<0.05);the alone NPM1 mutation occured in normal karyotype group was significantly higher CR than rate than NMP1~-patients(P=0.000,<0.05),The NMP1~+/FLT3/ITD~+patients of lower CR and short OS(P=0.039,<0.05),CEBPA mutation was more observed in FAB subgroup M2,CEBPA double mutation had significantly higher CR rate than CEBPA~-.but the OS had no difference(P=0.997,>0.05).6)Among the 175 AML patients,16 case were lost,NR were 43cases,98 cases of CR were treatment with consolidation therapy,The survival rates of 1 and 2 years were 39.79%(39/98)and 22.72%respectively;18 patients treat with hematopoietic stem cell transplantation after CR.The survival rates of 1 and 2 years were 100.0%and 50.0%respectively,and were obviously higher than not transplant patients(p=0.000,p=0.215),and hematopoietic stem cell transplantation can improve survival time.Conclusions:1)In AML,the common fusion gene were AML1/ETO?MLL(MLL/AF6?MLL/AF9?MLL/ENL?dup MLL)?HOX11?CBF?/MYH11?DEK/CAN?EVI1,the total positive rate was 36.57%;four kinds of mutation genes can been detect,the total positive rate was 44.49%;According to FAB classification,gene abnormality were more observed in FAB subgroup M2?M5;So we can chose to detect those high rate genes,and other 22 kinds of fusion genes can not detect.2)AML1/ETO expression was more observed in FAB subgroup M2 and have significantly high CR rate,but often combine with C-kit/D816 mutation witch can result relapse,hematopoietic stem cell transplantation shoud been recommend.3)Other genes,such as the EVI1~+often coexpression with MLL~+fusion gene;HOX11 expression had the tendency in old age patients;these rare genes weather affect the prognosis were not known.4)FLT3/ITD~+mutation had high peripheral WBC count,and the survival time of FLT3/ITD~+AML was short and were relative to poor prognosis.NPM1~+was easily merge with FLT3/ITD~+mutation,the alone NPM1 mutation occured in normal karyotype group and had significantly higher CR rate than NMP1~+/FLT3/ITD~+patients;CEBPA double mutation had significantly higher CR rate than CEBPA~-.and may relative to good prognosis in AML.5)After CR,compared with the consolidation therapy,the treatment with hematopoietic stem cell transplantation can improve survival time.Patients with poor prognosis should be treated with hematopoietic stem cell transplantation aggressively.