[Mutation of isocitrate dehydrogenase 2 (IDH2) gene in Chinese AML patients and its clinical significance]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Jun;21(3):607-12. doi: 10.7534/j.issn.1009-2137.2013.03.014.
[Article in Chinese]

Abstract

This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian People / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • Female
  • Genotype
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Karyotyping
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Remission Induction
  • WT1 Proteins / genetics
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • DNMT3A protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • WT1 Proteins
  • WT1 protein, human
  • Nucleophosmin
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3