Xing Guo1, Run Zhang1, Zheng Ge2, Jing-Yan Xu3, Min Li1, Chun Qiao1, Hai-Rong Qiu1, Jian-Yong Li1. 1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People Hospital, Nanjing 210029, Jiangsu Province, China. 2. 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. 3. Department of Hematology, The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China.
Abstract
BACKGROUD: 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). CONCLUSION: FBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.
BACKGROUD: 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). CONCLUSION: FBXW7 mutations may play an important role in NOTCH1 mediated pathogenesis in T-ALL.
Authors: Zheng Ge; Min Li; Gang Zhao; Lichan Xiao; Yan Gu; Xilian Zhou; Michael D Yu; Jianyong Li; Sinisa Dovat; Chunhua Song Journal: Oncol Lett Date: 2016-08-10 Impact factor: 2.967