Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Leukoc Biol. 2010 Jul;88(1):107-16. doi: 10.1189/jlb.1109748. Epub 2010 Apr 1.
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.
IL-7R、FLT3 和 CD43 是 BM 中前 B 细胞向 pre-B 细胞过渡期间表达的表面抗原。为了了解它们的信号通路之间的相互作用，我们分析了具有双 MLV 整合到 Stat5a 和 Fiz1 或 Stat5a 和 Hipk2 的自发小鼠 B-LBL。与 BM 中的正常前 B 细胞相比，MLV 整合导致淋巴瘤细胞中这些基因的上调。在同时整合到 Stat5a 和 Fiz1 的淋巴瘤中，在刺激 FLT3 后观察到磷酸化 STAT5A 的增加和 STAT5A 的靶基因 c-Myc 的表达。在含有 Stat5a 整合的克隆中，在添加了 IL-7 和 FLT3L 的培养基中生长更快，而在含有双整合的克隆中生长更快。另一方面，在同时整合到 Stat5a 和 Hipk2 的淋巴瘤中，在交联 CD43 后观察到磷酸化 STAT5A 的增加和 c-Myc 的表达。总之，FLT3 和 CD43 信号通路通过 Fiz1 和 Hipk2 在 B-LBL 中涉及 STAT5A。因此，鉴定 B-LBL 中的双 MLV 整合位点将为鉴定 B-LBL 中的信号通路提供一个极好的工具。
