Effects of IDH2 Gene Mutation on Clinical Characteristics and Prognostic of Patients with Acute Myeloid Leukemia.
10.19746/j.cnki.issn.1009-2137.2019.04.014
- Author:
Li-Qing LUO
1
;
Zhen-Yi PENG
2
;
Xiao LIU
1
;
Wen-Zheng YU
3
Author Information
1. Department of Hematology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China.
2. Department of Thyroid & Breast Surgery,, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China.
3. Department of Hematology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China,E-mail: yuwenzheng2009@163.com.
- Publication Type:Journal Article
- MeSH:
Genotype;
Humans;
Isocitrate Dehydrogenase;
genetics;
Leukemia, Myeloid, Acute;
Mutation;
Prognosis
- From:
Journal of Experimental Hematology
2019;27(4):1077-1082
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the prevalence, clinical characteristics and prognostic significance of the isocitrate dehydrogenase 2(IDH2) mutations in patients with acute myeloid leukemia(AML).
METHODS:The bone marrow samples of 223 patients with newly diagnosed AML confirmed by MICM typing from January 2015 to October 2018 were collected. The mutation of exon 4 of IDH2 gene was detected by direct sequancing of PCR product; the incidence and types of IDH2 gene mutation in AML patients were analyzed; the clinical characteristics of AML patients with IDH2 gene mutation were analyzed and the therapeutic efficacy for these patients was evaluated.
RESULTS:In a cohort of 223 AML patients, mutations were detected in 23(10.31％) patients, among them, 15 with R140Q mutations(65.22%) , 6 with R172K mutations(26.09%) and 2 with R140W mutations(8.70%). The median age in IDH2 mutated group was older than that in non.mutated group(P=0.008). The platelet level at initial diagnosis in IDH2 mutated group was higher than that in non.mutated group(P=0.010). There was no significant statistical difference between IDH2 mutated group and non.mutated group in FAB subtypes of AML(P>0.05). But the rate of IDH2 mutation in M4 and M5 was higher. The rate of IDH2 mutations was higher in AML with normal karyotype and in AML with NPM1 mutations. R140Q mutations associated with NPM1 mutations(χ=8.481，P=0.004), but R172K mutations not associated with NPM1 mutation(P>0.05). IDH2 mutated patients had a lower complete remission rate than non.mutated patients(57.14% vs 80.46%, χ=5.927，P=0.015). The complete remission rate of R140Q mutated patients was not significantly statistically different from non.mutated patients. The complete remission rate of R172K mutated patients was very significantly lower than non.mutated patients(χ=7.734，P=0.005). In the patients without NPM1 mutation, the 2 years overall survival in IDH2 mutated group was lower than in non.mutated group(36.36% vs 66.40%,χ=3.958，P=0.047), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In all patients, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(50% vs 66.88%,P>0.05), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In the patients with normal karyotype or with mutated NPM1, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(P>0.05).
CONCLUSION:IDH2 gene mutations are more common in AML patients at older age, higher platelets level and normal karyotype. The rate of IDH2 mutation in M4 and M5 is higher. IDH2 gene mutations associate with NPMl gene mutations, but R172K mutations not associates with NPM1mutation. IDH2 gene mutations associate with prognosis of AML patients, R140Q mutations have no effect on prognosis of patients, but R172K mutations may be the molecular markers for poor prognosis in AML patients.
