title: Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis.
abstract: BACKGROUND
  Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).
  
  
  METHODS
  Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.
  
  
  RESULTS
  In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
  
  
  CONCLUSIONS
  The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Yin
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Tong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human