title: The Frequency and clinical significance of IDH1 mutations in Chinese acute myeloid leukemia patients.
abstract: OBJECTIVE
  Mutations in the gene encoding isocitrate dehydrogenease 1 (IDH1) occur in various hematopoietic tumors including acute myeloid leukemia (AML), myeloproliferative neoplasms and myelodysplastic syndromes. IDH1 mutations are significant in both diagnosis and prognosis of these conditions. In the present study we determined the prevalence and clinical significance of IDH1 mutations in 349 samples from newly diagnosed AML patients.
  
  
  RESULTS
  Of the 349 AML patient specimens analyzed, 35 (10.03%) were found to have IDH1 mutations including 4 IDH1 R132 mutations and 31 non-R132 mutations. IDH1 non-R132 mutations were largely concentrated within AML-M1 (35.72%, p<0.01). We identified five IDH1 mutations that were novel to AML: (1) c.299 G>A, p.R100Q; (2) c.311G>T, p.G104V; (3) c.322T>C, p.F108L; (4) c.356G>A, p.R119Q; and (5) c.388A>G, p.I130V. In addition, we identified three IDH1 mutations that were previously described in AML. The frequency of IDH1 mutations in AML patients with normal karyotype was 9.9%. IDH1 non-R132 mutations were concurrent with mutations in FLT3-ITD (p<0.01), CEBPA (p<0.01), and NRAS (p<0.01), as well as the overexpression of MN1 (p<0.01) and WT1(p<0.01). The overall survival (OS) in the patients with IDH1 non-R132 mutations compared to patients without IDH1 mutations don't reach statistically significance (median 521 days vs median: not reached; n.s.).
  
  
  CONCLUSIONS
  IDH1 non-R132 mutations occurred frequently in newly diagnosed adult Chinese AML patients, and these mutations were associated with genetic alterations. The OS was not influenced by IDH1 non-R132 mutations in the present study.
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Lixun
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Hematology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Hematology and Hainan Branch, General Hospital of PLA, Beijing, China.
authors.forename: Chunji
authors.initials: C
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002648:Child; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D016019:Survival Analysis
chemical_list: D001120:Arginine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human