例如:"lncRNA", "apoptosis", "WRKY"

Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia.

Exp. Cell Res.2018 Oct 15;371(2):409-416. Epub 2018 Sep 01
Xiaoya Lu 1 , Haifeng Zhuang 2 , Qingfeng Yu 1 , Xuzhao Zhang 1 , Zhaoxing Wu 1 , Lei Zhang 1 , Ying Xu 1 , Bowen Wu 1 , Linlin Yang 1 , An Ma 3 , Xiaoxian Gan 3 , Xiaofang Yu 4 , Jianping Shen 5 , Rongzhen Xu 6
Xiaoya Lu 1 , Haifeng Zhuang 2 , Qingfeng Yu 1 , Xuzhao Zhang 1 , Zhaoxing Wu 1 , Lei Zhang 1 , Ying Xu 1 , Bowen Wu 1 , Linlin Yang 1 , An Ma 3 , Xiaoxian Gan 3 , Xiaofang Yu 4 , Jianping Shen 5 , Rongzhen Xu 6
+ et al

[No authors listed]

Author information
  • 1 Department of Hematology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China; Cancer Institute, Zhejiang University, Hangzhou 310009, China.
  • 2 Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou310009, China.
  • 3 Zhejiang Academy of Medical Sciences, Hangzhou 310012, China.
  • 4 Cancer Institute, Zhejiang University, Hangzhou 310009, China.
  • 5 Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou310009, China. Electronic address: sjping88@163.com.
  • 6 Department of Hematology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province), The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China; Cancer Institute, Zhejiang University, Hangzhou 310009, China; Institute of Hematology, Zhejiang University, Hangzhou 310009, China. Electronic address: zrxyk10@zju.edu.cn.

摘要


Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia. The UBA2-WTIP fusion gene contains the N-terminal E1_enzyme_family, VAE_Ubl domains of UBA2, and the C-terminal LIM domains of WTIP. The UBA2-WTIP fusion was detected by reverse transcriptase polymerase chain reaction and Sanger sequencing in 19 of 56 acute myeloid leukemia samples (33.9%). Ectopic expression of the UBA2-WTIP fusion in human acute myeloid leukemia KG-1a cells showed enhanced cell proliferation both in vitro and in vivo. The UBA2-WTIP fusion induced phosphorylation of and ERK1/2, and abrogates WTIP-mediated mammalian processing body formation. Finally, triptolide displayed selective cytotoxicity against KG-1a cells harboring the UBA2-WTIP fusion. Collectively, our findings suggest that the UBA2-WTIP fusion is an oncogenic fusion gene, as well as a promising therapeutic target for the treatment of acute myeloid leukemia.

KEYWORDS: Acute myeloid leukemia, Fusion gene, UBA2, WTIP