Analysis Of DNMT3A Gene Mutation In 342 Patients With Acute Myeloid Leukemia And Its Clinical Significance

Objective:To study the frequency and form of mutation of methylation-related gene DNMT3 A in patients with acute myeloid leukemia(AML)and its clinical significance.Methods:Collected 342 patients with AML(non-APL)fresh specimens of bone marrow mononuclear cells were isolated by extracting its genomic DNA,and then used PCR and other techniques for gene sequence detection.Analysis of SPSS18.0 Statistical Software was used to analysis the correlations of the DNMT3 A expression with the clinical features of AML,affecting the efficacy of chemotherapy and other common gene mutations.Results:1.In a total 342 AML(non-APL)patients,83 AML(non-APL)patients(24.3%)were identified with DNMT3 A mutations.The distribution of mutations was as follows:R882H(n=48,57.8%),R882C(n=16,19.3%),R882P(n=3),R882H/C(n=1),L905Q(n=1),N879D(n=1),L901F(n=1),others(n=12).2.In 342 AML(non-APL)patients,there was significant difference in sex to DNMT3 A mutations,was statistical difference(P = 0.002).3.The patients were divided into three age groups(≤40y、41-65y、≥66y).DNMT3 A mutation rate was the highest in 41-65 age(mid-life)group,and there was statistical difference to DNMT3 A mutations in age(P=0.020).4.Base on French-American-British(FAB)criteria,in 342 AML(non-APL)patients DNMT3 A mutations had statistical significance(P<0.001).More M4 and M5 patients were observed in DNMT3 A mutated group compared to others.5.In patients,no statistical differences were observed in BM blast(P=0.320)and hemoglobin counts in PB(P=0.987)between mutant and wild type patients,while there was significant difference in platelet counts(P<0.001)between patients with and without DNMT3 A mutations.There were DNMT3 A mutations in AML(non-APL)patients with high white blood cell count,but no statistical significance(P= 0.196).6.There were no statistical significance in the expression of DNMT3 A mutation between FLT3-ITD and FLT3-TKD mutant and wild type patients(P>0.05).There were statistical differences in the expression of DNMT3 A mutation among CEBPA,NPM1 andc-KIT mutated group and wild type patients(P<0.05).7.The percentage of DNMT3 A mutations was significantly higher in patients with normal karyotype AML(non-APL)than in those with karyotype abnormality(P<0.001).The chromosomal karyotype analysis of 342 patients with AML(non-APL)showed a statistically significant difference(P<0.001).8.For the treatment of 342 patients with AML(non-APL)analysis,there were no significant differences in the efficacy of the first induction chemotherapy(P=0.224)between 83 patients with DNMT3 A mutations and 259 patients with DNMT3 A wild type.The 83 patients with DNMT3 A mutations were treated with chemotherapy for one cycle,which were analyzed in the curative effect of multivariate.The FAB was effective in the treatment of AML patients with DNMT3 A mutation(P<0.05).There were significant differences in the patients of AML(non-APL)DNMT3A mutations with and without NPM1 mutations,which had been receiving the first induction chemotherapy cycle(P<0.05).Conclusion:1.The result revealed that gender,age,peripheral blood platelet count,FAB classification,chromosome karyotype,CEBPA,NPM1,c-KIT gene mutations were associated with DNMT3 A mutations in AML(APL)patients,while white blood cell count,hemoglobin count in peripheral blood and bone marrow in primitive cell count,FLT3 ITD and FLT3 TKD mutations were not associated with DNMT3 A mutations in AML(non-APL)patients.2.The differences of the FAB distributions were observed in DNMT3 A mutations in AML(non-APL)patients,which mainly related to the M4,M5.3.Between DNMT3 A mutations type and wild type in AML(non-APL)patients received the first induction alleviate chemotherapy;Treatment effect was no statistical siginificance.Treatment effect of DNMT3 A mutations in AML(non-APL)patients receiving the first induction chemotherapy cycle,was associated with FAB classification and expression of NPM1 mutations,which has statistical significance.