Study On The Mutations Of NPM1 And IDH1/IDH2 Gene In Neoplastic Hematologic Disorders

Objective Through the analysis of gene mutation, this paper discusses NPM1 and IDH1/IDH2 gene mutation rate and distribution in Chinese patients with hematological malignancies, and analyze the clinical features, prognosis, and analyze the correlation between genetic mutations.Method Collect in April 2013-may 2014 in the First Affiliated Hospital of Kunming Medical University from Department of Hematology in 304 patients with different types of blood cancerbone marrow samples. Adopt the method of PCR combined with gene sequencing to detect the NPM1 gene in patients with hematologic malignancies were exon exon 12, exon 4 of IDH1/IDH2 gene mutation.Result 304 cases with different blood cancer patients(138 cases of AML,39 cases of ALL,43 cases of CML,16 cases of CLL,15 cases of MDS,22 cases of MM,31 cases of NHL) of NPM1, IDH1/IDH2 mutations in hematologic malignancies distribution characteristics are as follows:1. The relapsed or refractory AML and ALL group age was significantly higher than that of AML and ALL in complete remission group, and the difference was significant.2.41 cases of newly diagnosis in patients with AML, NPM1 mutations detected in 5 cases, the mutation rate is 12.20%, the mutation type was A and B, in patients with NK-AML mutation rate was 21.43% and the normal karyotype group mutation rate was significantly higher than that of abnormal karyotype group, but no significant differences; 37 cases of relapse or refractory AML, NPM1 mutations detected in 1 cases, the mutation rate was 2.7%, the mutation is A type; no mutations in AML-CR patients. Newly diagnosed patients with AML mutation rate is significantly higher than that in AML-CR group, and the difference was significant; in experiment, monitoring to 1 cases of newly diagnosed patients with NPM1 mutation, after complete remission the NPM1 mutation was negative. Newly diagnosed group and the relapse or refractory group of patients with NPM1 mutations and wiled type patients in age, sex, white blood cell, hemoglobin, platelet, the proportion of bone marrow original cells, the FAB type had no significant difference. Newly diagnosed patients with AML mutations and wild type were 2 CR treatment rate had no significant difference.In the ALL, CML, CLL, MDS, MM, NHL patients were not found with NPM1 gene mutation.3.41 cases of newly diagnosed AML patients were not detected in the IDH1/IDH2 gene mutation; 37 cases of relapsed or refractory AML patients with IDH1 mutations were detected in 3 cases, the mutation rate was 8.11%, the types of mutations:p.R132H, p.R132C (missense mutations), p.G105G (synonymous mutation),2 case of IDH2 mutation, the mutation rate was 5.41%, the mutation types:p.R172K(missense mutations), the total mutation rate of IDH was 13.51%; 60 cases of AML-CR were found in 1 cases of missense mutations in IDH2:p.P167R; the relapse or refractory group IDH mutation rate was significantly higher than that of newly diagnosed AML, the mutation rate between the two groups have significant differences; in experiment, monitoring to 1 cases of replase patients with IDH1 mutation, and in again after induction of remission has become IDH2 mutation. The relapse or refractory group of patients with the mutation and wild type patients in age, sex, white blood cell, hemoglobin, platelet, the proportion of bone marrow original cells, the FAB type had no significant difference.In 16 cases of newly diagnosed ALL,15 cases of ALL-CR were not found in patients with IDH1/IDH2 mutations,8 patients with relapse or refractory ALL were found in 2 cases of IDH1 gene mutation, the mutation rate was 25%,1 cases of IDH2 gene mutation, the mutation rate was 12.5%, the total mutation rate of IDH was 37.5%. The relapse or refractory group IDH mutation rate is significantly higher than that in newly diagnosed group and CR group, there was significant difference in mutation rate. The relapse or refractory group of patients with the mutation and wild type patients in age, sex, white blood cell, hemoglobin, platelet, the proportion of bone marrow original cells, the FAB type had no significant difference.31 patients with NHL were found in 1 case of IDH1 gene missense mutation(p.R132H), according to 2008 world health organization (WHO) classification standard of peripheral T-cell lymphoma(unspecified).It was not reported in the world.In the CML、CLL、MDS、MM patients were not found with IDH1/IDH2 mutation.4.41 cases of newly diagnosed AML patients were found 2 cases of NPM1 mutations combine with FLT3-ITD mutations,37 cases of relapsed or refractory AML patients were found 1 case of NPM1 mutations combine with IDH1 mutations, other combination mutations were not found.Conclusions1. NPM1, IDH1/IDH2 gene mutation mainly occurred in AML patients, rare mutations in other hematologic malignancies, is an important molecular marker of AML.2. NPM1, IDH1/IDH2, FLT3-ITD gene frequently combination mutations, different forms of joint mutation are closely related prognosis.3. NPM1, IDH1/IDH2 gene mutation can be used as MRD monitoring indicator of AML patients.4. In patients with relapse or refractory leukemia has high frequency of IDH1/IDH2 gene mutation, it is a sign of relapse or refractory and poor prognosis.5. IDH1 gene mutations can occur in peripheral T-cell lymphoma(unspecified), maybe an indicator of poor prognosis, we monitored the cases in the world unreported, worthy of further intensive study.