Semaphorin4D通过MAPK/ERK信号通路调控急性淋巴细胞白血病细胞增殖及凋亡的作用研究

急性淋巴细胞性白血病(Acute lymphoblastic leukemia ，ALL)是一种最常见的儿童血液系统恶性肿瘤。我们前期研究发现Semaphorin4D（Sema4D）分子在源于ALL的Jurkat细胞及部分ALL患者骨髓和外周血肿瘤细胞异常高表达，转录组测序发现Jurkat细胞内MAPK分子的表达与Sema4D正相关。因此,我们推测Sema4D可能通过MAPK信号通路调控ALL细胞的增殖凋亡等生物学行为。本研究拟利用慢病毒感染过表达及干扰、免疫共沉淀及质谱等细胞信号传导技术手段研究Sema4D异常表达对ALL细胞增殖及凋亡等生物学行为的影响，探索Sema4D通过MAPK\ERK信号通路调控ALL细胞增殖、凋亡的作用机制，发现信号通路中参与Sema4D调控的关键分子，并通过构建小鼠移植瘤模型进行验证。本研究将初步阐明Sema4D调控ALL细胞增殖、凋亡等生物学行为的机制。

Acute lymphocytic leukemia（ALL）is the most frequently malignant hematological tumor which occurs in children, and the pathogenesis of ALL still need to be explored. Our study found that Semaphorin 4D (Sema4D) is highly expressed in ALL cells and tumor cells in bone marrow from 46.7% ALL patients, which provided that the Sema4D may be related to the development of ALL. In this study we will explore the role of Sema4D both in ALL cell lines on cell proliferation, cycle and apoptosis. Meanwhile, our research will plan to explore the role of Sema4D in molecules of MAPK\ERK Pathway in ALL cell lines and nude mice, which will provide solid basis for the mechanisms on cell proliferation, cycle and apoptosis targeting Sema4D in ALL. Our research will provide a potential target for the future treatment for ALL.