title: TET2mutations were predictive of inferior prognosis in the presence ofASXL1mutations in patients with chronic myelomonocytic leukemia.
abstract: BACKGROUND
  Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus thatASXL1mutations have adversely impact on overall survival (OS), while the effect ofTET2mutations remains controversial and undefined.
  
  
  METHODS
  ASXL1andTET2mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay ofASXL1andTET2mutations in the prognosis of CMML.
  
  
  RESULTS
  Sixty-five (46.1%) of the CMML patients harbored ASXL1 mutations (frameshift and nonsense), and 46 (32.6%) had TET2 mutations (frame shift, nonsense and missense). In a separate multivariable analysis that included the Mayo Prognostic Model as a single variable along withASXL1wt/TET2wt, the respective hazard ratios ofASXL1mut/TET2mut,ASXL1mut/TET2wt andASXL1wt/TET2mut were 4.7 (95% CI, 2.2-10.3; P<0.001), 2.2 (95% CI, 1.1-4.2; P=0.025) and 1.3 (95% CI, 0.6-2.5; P=0.521).
  
  
  CONCLUSIONS
  Our study showed thatASXL1mutations predict inferior OS, and additionalTET2mutations were associated with poor survival in the presence ofASXL1mutations of CMML patients.
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Yajuan
authors: Y
authors: Cui
authors: Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310000, China.
authors: Hongyan
authors: H
authors: Tong
authors: Department of Hematology, Guangdong General Hospital, Guangzhou 510010, China.
authors: Xin
authors: X
authors: Du
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Bing
authors: B
authors: Li
authors: Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK.
authors: Robert Peter
authors: RP
authors: Gale
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Tiejun
authors: T
authors: Qin
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Jinqin
authors: J
authors: Liu
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Zefeng
authors: Z
authors: Xu
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Yue
authors: Y
authors: Zhang
authors: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Gang
authors: G
authors: Huang
authors: Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310000, China.
authors: Jie
authors: J
authors: Jin
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Liwei
authors: L
authors: Fang
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Hongli
authors: H
authors: Zhang
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Lijuan
authors: L
authors: Pan
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Naibo
authors: N
authors: Hu
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Shiqiang
authors: S
authors: Qu
authors: MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors: Zhijian
authors: Z
authors: Xiao
keywords: ASXL1 mutations; TET2 mutations; chronic myelomonocytic leukemia (CMML); prognosis