title: [Mutations of FBXW7 in Adult T-Cell Acute Lymphocytic Leukemia].
abstract: BACKGROUND
  F-Box and WD40 domain containing protein 7 gene (FBXW7) is part of the E3 ubiquitin ligase complex that controls the turnover of various proteins including NOTCH1, c-MYC and Cyclin E.
  
  
  OBJECTIVE
  To investigate the mutations of FBXW7 gene in adult T-cell acute lymphoblastic leukemia (T-ALL).
  
  
  METHODS
  Exon 5-12 of FBXW7 were amplified, cloned and sequenced in 54 adult T-ALL patients; the frequency, position and types of FBXW7 mutation were analyzed; the co-existing of mutations with NOTCH1 and their relevant prognostic significance were explored as well.
  
  
  RESULTS
  FBXW7 mutations were identified in 11.1% of adult T-ALL patients. A total of 4 types of point mutations (R465H, R465L, R479P and R505C) and 1 deletion/insertion mutation were observed, and all of them located in WD40 domain of FBXW7. In addition, co-existing mutations with NOTCH1 were identified in 83.3% of patients with FBXW7 mutation. Notably, the co-existed NOTCH1 mutations, including 3 point mutations (L1574P, L1596H and L1600P) and 2 deletion/insertion mutations located in HD domain. Furthermore, patients with FBXW7 mutation only had significantly longer overall survival compared with those without mutation (P=0.049).
  
  
  CONCLUSIONS
  FBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China. E-mail: Gezheng2008@163.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Hematology, The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Qiu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins; D005091:Exons; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D016259:Genes, myc; D006801:Humans; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases