title: [IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia].
abstract: OBJECTIVE
  To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.
  
  
  METHODS
  Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.
  
  
  RESULTS
  Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).
  
  
  CONCLUSIONS
  The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Wei
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Qiu
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Chen
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Mao
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jia
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Lian-Guo
authors.initials: LG
authors.lastname: Xue
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Zhi-Mei
authors.initials: ZM
authors.lastname: Cai
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China.
authors.forename: Yuan-Xin
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Lianyungang First People's Hospital, Jiangsu Institute of Hematology, Lianyungang 222000, Jiangsu Province, China. E-mail: zld060201@sina.com.
authors.forename: Li-Dong
authors.initials: LD
authors.lastname: Zhao
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D005091:Exons; D006579:Heterozygote; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D007958:Leukocyte Count; D009154:Mutation; D020125:Mutation, Missense; D000090243:Nucleophosmin; D010976:Platelet Count; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human