title: [Relationship between clinical characteristics and myelodysplastic syndrome patients with isocitrate dehydrogenase gene mutations].
abstract: OBJECTIVE
  To assess the prevalence and clinical characteristics of isocitrate dehydrogenase 1 and 2 (IDH 1 and IDH2) gene mutations in myelodysplastic syndrome (MDS) patients.
  
  
  METHODS
  Pretreatment bone marrow specimens were enriched for mononuclear cells in 108 adult patients with de novo MDS from January 2006 to August 2012. Genomic DNA was extracted from mononuclear cells. And PCR and direct sequencing were performed to sequence exon 4 of IDH gene.
  
  
  RESULTS
  IDH mutations were discovered in 11 MDS patients (10.19%, 11/108) and all were heterozygous. The frequencies of IDH1 and IDH2 mutations were 5.56% (6/108) and 4.63% (5/108) respectively. Only one type of IDH1 mutation (c.394C→, p.R132C) was identified in our cohort. All IDH2 mutations caused the changes of R140 (c.419G→A, p.R140Q). However IDH2 R172 mutation was not detected. The combined mutations of IDH1 and IDH2 were not simultaneously observed in the same patient. The prevalence of IDH mutation was higher in advanced-stage MDS than those early-stage MDS patients. Mutated and wild-type groups had significantly difference in bone marrow blast percentage (median 12.5% vs 6.0%, P = 0.013) at diagnosis, but not in white blood cell count, hemoglobin level and platelet count, etc. In the normal karyotype group, the frequencies of IDH mutations were as similar as those in the abnormal karyotype group (10.61% (7/66) vs 10.00% (4/40), P > 0.05). The median follow-up time was 472 d, our data indicated that IDH mutations were correlated with poor overall survival (median time 512 vs 740 d, P = 0.017). IDH mutations were also an inferiorly predictive factor in the intermediate-1 group patients of International Prognostic Scoring System (IPSS) (median survival time 512 d vs not reached, P = 0.038). There was also better efficacies than other treatments in IDH mutation positive patients (median survival time 623 vs 165 d, P = 0.049).
  
  
  CONCLUSIONS
  IDH mutation is a vital biomarker for better risk stratification of MDS patients with and improving IPSS. Hypomethylation agents may be effective for treating IDH mutation positive patients.
authors.affiliation: Department of Hematology, Myelodysplastic Syndromes Diagnosis and Therapy Center, First Affiliated Hospital of Zhejiang University, Institute of Hematology, Key Laboratory for Hematology of Zhejiang Province, Hangzhou 310009, China.
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Tong
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.forename: Meng-xia
authors.initials: MX
authors.lastname: Yu
authors.forename: Qiu-ling
authors.initials: QL
authors.lastname: Ma
authors.forename: Fei-fei
authors.initials: FF
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Ju-ying
authors.initials: JY
authors.lastname: Wei
authors.forename: Gai-xiang
authors.initials: GX
authors.lastname: Xu
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Mao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Email: zjuhematology@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human