title: IDH2 mutations are frequent in Chinese patients with acute myeloid leukemia and associated with NPM1 mutations and FAB-M2 subtype.
abstract: BACKGROUND
  Gene mutations play an important role in acute myeloid leukemia (AML) pathogenesis. Several genes have been identified in AML, such as FLT3, KIT, NPM1, and JAK2. This study investigated the frequency of novel mutations in IDH1 (amino acid R132) and IDH2 (R140 and R172) and analyzed their impact on disease biology and interaction with other mutations in Chinese patients with de novo AML.
  
  
  METHODS
  A total of 195 patients were screened for mutations in the IDH1, IDH2, JAK2 V617F, NPM1, FLT3, and KIT genes, using polymerase chain reaction (PCR)-based and direct sequencing assays.
  
  
  RESULTS
  IDH mutations occurred at a considerable frequency of 15.89% in Chinese AML cases; IDH2 R140Q was the most frequent genetic alteration and was associated with older age, normal karyotype, and French-American-British classification M2 at diagnosis. There was a strong association of IDH2 mutation with NPM1 mutations and a trend with FLT3-internal-tandem duplication.
  
  
  CONCLUSIONS
  IDH mutations may be a novel genetic marker in cytogenetically normal AML and may cooperate in leukemogenesis.
authors.affiliation: Department of Hematology, Affiliated Changzhou Second Hospital of NanJing Medical University, Changzhou, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chao
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Jia
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Lu
authors.forename: L
authors.initials: L
authors.lastname: Cen
authors.forename: R
authors.initials: R
authors.lastname: Xiao
authors.forename: N-K
authors.initials: NK
authors.lastname: Jiang
authors.forename: J-H
authors.initials: JH
authors.lastname: Ying
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.forename: R
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3; D053614:Janus Kinase 2