| Objective:Acute myeloid leukemia is a highly heterogeneous clonal tumor of malignant blood system.Gene mutation has important guiding significance for the diagnosis,treatment options and prognosis of AML.Approximately 95% AML patients can detect at least one somatic cell gene mutations.DNMT3 A mutation is prevalent in adult AML with an incidence of about 14% to 34%.Compared with wild-type DNMT3 A patients,they be frequently diagnosed with normal karyotype with monocytic(French-American-British M4 and M5)blast morphology.The coding region in AML reported that around 60% of DNMT3 A mutations are found at the residue R882 in the methyltransferase domain,and the most one is R882 H.DNMT3A mutanted patients tend to be older,have higher white blood counts and bone marrow blasts.The prognostic significance of DNMT3 A mutations is currently controversial.Most of them believe that DNMT3 A mutations are associated with poor prognosis in patients with AML,but a few studies have reported that DNMT3 A mutations cannot be used as independent prognostic markers in overall and specific subgroup AML patients.Two-hundred and ninety-six patients with de novo AML were retrospectively analyzed with regard to the impact of DNMT3 A gene mutation on the clinical characteristics and prognoses in our hospital.Methods:Retrospective analysis of 296 cases of de novo AML from the Cancer Center,First Hospital,Jilin Universisty during the period from 2015.12 to 2017.10.3ml of the bone marrow specimens was collected before treatment,and then detected the histology,cytogenetics and molecular biology.The basic clinical data of the patients were collected in the initial treatment,including age,sex,peripheral white blood cells,hemoglobin and platelet levels,and bone marrow blasts and then analyse the clinical characteristics and prognoses of the patients with DNMT3 A gene mutation.Results:In total,we identified seventy-seven DNMT3 A mutations(26.01%)in twohundred and ninety-six patients with de novo AML.Of the seventy-seven patients with DNMT3 A mutations,fifty-three cases(53/68,68.83%)were R882 mutations.The karyotype was successfully analyzed in 235 patients.The incidence of DNMT3 A mutation was 33.33%(52/156)in 156 normal karyotype patients,and the incidence of DNMT3 A mutation was 5.06%(4/79)in 79 patients with abnormal karyotype.The DNMT3 A mutation co-mutation rate was 100%,often accompanied by NPM1 mutations and FLT3-ITD mutations,and fewer CEBPA double mutation occurred.Compared with DNMT3 A wild-type patients,patients with DNMT3 A mutations were associated with older age at diagnosis,higher peripheral white blood cell count,higher hemoglobin,and higher bone marrow blasts.The 2 course of induction remission rate of patients with DNMT3 A mutation was lower than that of DNMT3 A wild type patients,but the difference was not statistically significant(P = 0.271).The 2 year RFS of patients with DNMT3 A mutation were significantly lower than those of wild-type DNMT3 A patients,while no difference in2 year OS.In younger(<60 years)AML patients,the 2 year RFS of patients with DNMT3 A mutation were significantly lower than those of wild-type DNMT3 A patients(P= 0.010),while no difference in 2 year OS(P = 0.051).The 2 year OS and RFS of patients with R882-DNMT3 A mutation were higher than those of patients with non-R882-DNMT3 A mutation,but the difference was not statistically significant(P = 0.339;P = 0.592).DNMT3 A mutations patients within the NK-AML subset were associated with significantly lower 2 year OS and RFS compared to those the wild-type DNMT3 A patients(P = 0.005;P = 0.007).The 2 year RFS and OS of the DNMT3A-mutated group with NPM1 mutation were significantly higher than that of the DNMT3A-mutated group without NPM1 mutation(P = 0.037;P = 0.039).The2 year OS and RFS of the DNMT3A-mutated group with FLT3-ITD mutation was significantly lower than that of the FLT3-ITD-mutated group without DNMT3 A mutationan had a lower tendency than that of the DNMT3A-mutated group without FLT3-ITD mutation(P = 0.043;P= 0.093).The patients concomitant DNMT3 A,FLT3-ITD and NPM1 mutation had a lower tendency than that of those DMNT3Aothers-mutated patients and the wild-type DNMT3 A patients(P = 0.082).Univariate analysis showed: In AML,the factor that affecting OS was age,the factor that affect RFS were age and CEBPA double mutation.In NK-AML,the factor that affecting OS was age,and the factors that affect RFS were DNMT3 A mutation.Multivariate analysis showed that age was an independent prognostic factor for OS(P = 0.001),and CEBPA double mutation was an independent prognostic factor for RFS(P = 0.003)in AML.In NK-AML,age was an independent prognostic factor affecting OS,and DNMT3 A mutation was an independent prognostic factor affecting RFS.Conclusions:1.The incidence of DNMT3 A mutation in this group was 26.01%.DNMT3 A is mainly R882 mutation and the most one is R882 H.The DNMT3 A mutation is mainly found in the M4/M5 subtype of FAB and normal karyotype AML.The incidence of co-mutation in patients with DNMT3 A mutations is 100%,often accompanied by NPM1 mutations and FLT3-ITD mutations,and fewer CEBPA double mutations.Compared with DNMT3 A wild-type patients,patients with DNMT3 A mutations were associated with older age at diagnosis,higher peripheral white blood cell count,higher hemoglobin,and higher bone marrow blasts.2.There is no significant difference in the 2 course of induction remission rate between the DNMT3 A mutation patients and wild-type DNMT3 A patients.3.Survival analysis shpwed: DNMT3 A mutation accompanied by NPM1 mutation can attenuate the poor prognoses of DNMT3 A mutation.DNMT3 A mutation and the FLT3-ITD mutation have a synergistic effect on the poor prognosis of AML.DNMT3A/NPM1/FLT3-ITD mutation is an independent prognostic subtype.When NPM1 mutation coexists with DNMT3 A mutation and the FLT3-ITD mutation,the prognostic benefit of the NPM1 mutation is offset.4.Multivariate analysis showed that DNMT3 A mutation was an independent prognostic factor affecting RFS in NK-AML. |
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