伯基特淋巴瘤是一种B细胞非霍奇金淋巴瘤，增殖快、倍增时间短，应用目前的各种治疗方案仍有部分患者没有很好的疗效。我们前期研究工作发现与增殖相关的蛋白激酶JAK2和PBK/TOPK在大部分伯基特淋巴瘤中激活或高表达，JAK2可以结合PBK/TOPK，并能够磷酸化PBK/TOPK的Tyr74位点，表明二者的相互作用可能在伯基特淋巴瘤的增殖中起到重要作用，PBK/TOPK可能是淋巴因子-JAK-STAT信号途径与MAPK途径之间相互作用的关键点，JAK2和PBK/TOPK也可能是伯基特淋巴瘤治疗新的分子靶点。本课题拟采用分子生物学和动物实验的方法，探究JAK2磷酸化PBK/TOPK的相互作用对伯基特淋巴瘤增殖的影响以及二者相互作用的下游分子，研究这两种蛋白激酶是否可以作为治疗伯基特淋巴瘤的靶向分子。

Burkitt’s lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma and the fastest growing human tumor. Though the current treatment is effective for most of patients, there is still a portion of patients cannot be cured. We found that nearly 100% of the Burkitt’s lymphoma tumor cells are positive for PBK/TOPK and active form phospho-JAK2, JAK2 can bind PBK/TOPK in Burkitt’s lymphoma cells, and JAK2 can phosphorylate the Tyr74 site of PBK/TOPK. Based on the important role of PBK/TOPK in the cell cycle G2/M phase, we hypothesized that the interaction of JAK2 and PBK/TOPK may play an important role in the proliferation of Burkitt’s lymphoma, and may mediate the cross-talk of JAK-STAT pathway and MAPK pathway, JAK2 and PBK/TOPK are promising molecular targets of Burkitt’s lymphoma treatment. This project will focus on exploring the role of JAK2 - PBK/TOPK interaction in the proliferation of Burkitt’s lymphoma, the downstream protein of the interaction, and the application of JAK2 and PBK/TOPK inhibitor in the treatment of Burkitt’s lymphoma.