IGFBP2信号通路介导的AML髓外浸润机制研究

Extramedullary infiltration easily leads to the relapse of acute myeloid leukemia (AML) and thereby the death of patient, so it becomes a poor marker in AML. It is thus imperative to identify the key signaling pathway that regulate the extramedullary infiltration of AML. Target treatment of the key molecules by IGFBP2 signaling pathway would improve the long-time survival of the patients. Previous study suggested that IGFBP2 supports the migration of acute leukemia cells. However, the migration mechanism still remains elusive, which needs to be addressed and elucidated in this research proposal. According to previous study, we propose to utilize AML1-ETO9a fusion oncogene induced AML mouse model, combined with IGFBP2 knockout mice to explore the possible roles of IGFBP2 in the extramedullary of AML. We will systematically analyze the molecular network by which IGFBP2 facilitates the migration of AML. Also we will evaluate the migration change of AML caused by modifying the expression levels of some key signaling molecules. These systemically designed experiments will therefore provide important insight into the prognosis judgement and targeted treatment of AML.

髓外浸润是急性髓系白血病（AML）复发与患者死亡的重要因素，寻找靶向AML髓外浸润的相关信号通路有助于预防AML复发，提高疗效。研究表明胰岛素样生长因子结合蛋白2（IGFBP2）促进了AML髓外浸润，但IGFBP2促进AML髓外迁移的机制未明。我们拟在AML1-ETO9a癌基因建立的AML鼠模型基础上，结合IGFBP2敲除鼠，以AML细胞为研究对象，利用新一代转录组学解析技术，系统分析IGFBP2促进AML细胞髓外迁移的分子网络，进一步对关键效应分子的表达水平进行人为调控，评估其对AML髓外迁移的影响，为通过靶向IGFBP2关键通路治疗AML提供理论依据。