Clinical Characteristics And Prognosis Of Acute Myeloid Leukemia Patients With NPM1 And DNMT3A/FLT3-ITD Mutation

Objective:Acute myeloid leukemia(AML)is a group of heterogeneous diseases.Abnormal gene alterations can indicate the etiology of disease and provide guidance for the treatment options and prognosis.With the rapid development of high throughput sequencing technology,over 95% AML patients can detect at least one somatic cell gene mutation and each patient has about 12 genetic changes,in which an average of 3 driving gene mutations.NPM1 mutation is the most common gene mutation in adult AML,with an incidence of about 35%,while the incidence of AML in patients with normal karyotype can be as high as 50% to 60%.The frequencies of NPM1,DNMT3 A and FLT3-ITD were higher in newly diagnosed AML patients.We studied the NPM1 mutation positive AML patients in our hospital retrospectively to explore the impact of DNMT3A/FLT3-ITD gene mutation on the clinical characteristics and prognosis of patients.Methods:Retrospective analysis of 108 cases of AML with NPM1 mutation from the Cancer Center,First Hospital,Jilin University during the period from 2010.8 to 2017.11.3ml of the bone marrow specimens was collected before treatment,and then detected the histology,cytogenetics and cellular immunology.The basic clinical data of the patients were collected in the initial treatment,including sex,age,peripheral blood leukocytes,hemoglobin and platelet levels,and then analyse the clinical characteristics and prognosis of the patients with different mutation groups.Results:1.NPM1 has the highest proportion of A mutation,while DNMT3 A is mainly R882 mutation,and the most one is R882H?2.There was no significant difference in the mutation rate of FLT3-ITD in DNMT3 A positive and negative patients,and there was no significant correlation between the mutation and DNMT3 A mutation subtypes.3.White blood cells in patients with DNMT3A/FLT3-ITD mutation were significantly higher than those without mutation at the initial diagnosis.4.When NPM1 mutation occurred,whether DNMT3A/FLT3-ITD mutate or not did not affect the 1 course of induction remission rate?5.The 4 year RFS and OS of patients with NPM1 and DNMT3 A R882 mutation were higher than those of DNMT3 A non R882 mutation patients.6.With only NPM1 and DNMT3 A mutation had the highest RFS and OS,and the long-term prognosis of the other groups was similar.Conclusions:1.The main type of NPM1 mutation in first diagnosed AML patients was type A mutation,which was highly correlated with mononuclear leukemia and most of the patients were normal karyotype;DNMT3A mutation was mainly R882 mutation and was mainly R882H;the proportion of mononuclear leukemia in NPM1/DNMT3 A double mutation was higher.2.Compared with the single mutation of NPM1,the first diagnosis of NPM1/FLT3-ITD double mutation and NPM1/ DNMT3A/FLT3-ITD three mutation was higher in the first diagnosis of the leukocytes,and the platelets of the patients with NPM1/DNMT3 A double mutation were higher.3.The prognosis of AML patients with NPM1/DNMT3 A double mutation is better than that of NPM1 single mutation,NPM1/FLT3-ITD double mutation and NPM1/DNMT3A/FLT3-ITD three mutation.