Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in the IL-7 signaling pathway in B lymphoblastic lymphomas

Journal of Leukocyte Biology

Kazuya Kanaya²  Tatsuaki Tsuruyama³  Tomoko Okuno³  Guang Jin¹  Haruya Takeuchi³  Keiji Tamaki³  Yasuhiro Maruyama²  Hiroshi Hiai⁵  Tetsuya Takakuwa²  Takuya Hiratsuka⁴  Toshiaki Manabe⁴  Richard Kaszynski³  Yukiko Imai³  Munetaka Ozeki³  Takuro Nakamura¹ 

[1] Laboratory of Carcinogenesis, Cancer Institute, Tokyo, Japan; and Laboratory of Carcinogenesis, Cancer Institute, Tokyo, Japan; and Laboratory of Carcinogenesis, Cancer Institute, Tokyo, Japan; andDepartment of Human Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Human Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Human Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan;;Department of Forensic Medicine and Molecular Pathology, Department of Forensic Medicine and Molecular Pathology, Department of Forensic Medicine and Molecular Pathology,;Department of Diagnostic Pathology, and Department of Diagnostic Pathology, and Department of Diagnostic Pathology, and;Shiga Medical Center Research Institute, Shiga, Japan Shiga Medical Center Research Institute, Shiga, Japan Shiga Medical Center Research Institute, Shiga, Japan

关键词: murine leukemia;    Stat5a;    B-LBL;    Flt3;    CD43;   

DOI  :  10.1189/jlb.1109748

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs.

【 授权许可】

Unknown