Wnt/β-catenin信号通路在骨髓基质细胞对急性淋巴细胞白血病保护中的作用及机制研究

Acute lymphoblastic leukemia (ALL) is one of the hematological malignancies with high level of relapse, resistance to treatment and low survival rate. Increasing evidence suggests that relapse of the disease and resistance to treatment are largely attributed to the protection of the leukemic cells by various components in the microenvironment, such as marrow stromal cells (MSCs). However, the cross-talk between leukemic cells and their microenvironment remains poorly understood. In our previous study, we found MSCs could inhibit drug-induced apoptosis of primary ALL cells and ALL cell lines, and Wnt/β-catenin signaling pathway might be involved in the process. This project will be performed on the basis of previous study,by testing the molecular expressions of Wnt/β-catenin signaling pathway in ALL cells and MSCs form ALL patients, to analyze whether they are associated with therapy and prognosis;comparing the effects of normal MSCs and patient MSCs on ALL cell survival and response to chemotherapy, to better understand the significance of MSCs in ALL and the role of Wnt/β-catenin pathway in the interaction of MSCs and ALL cels, which will develop new theories and therapies disrupting such protection.

急性淋巴细胞白血病（ALL）是一种常见恶性血液病，大多数病人容易复发和产生耐药，整体生存率低。越来越多的证据表明ALL的复发和耐药与骨髓微环境如基质细胞（MSCs）有关，但白血病细胞及微环境相互作用的机制还不清楚。本课题组前期研究发现MSCs可抑制化疗药诱导的ALL细胞凋亡,并且Wnt/β-catenin信号通路可能在其中发挥重要作用。本项目拟在已有的工作基础上，检测Wnt信号通路在患者ALL细胞及MSCs的表达情况，分析其与临床疗效及预后的关系；通过比较正常的MSCs及患者的MSCs对ALL细胞的影响，进一步阐述MSCs在ALL耐药中的意义，明确Wnt/β-catenin信号通路在MSCs和ALL细胞相互关系中的具体作用，为阻断微环境对ALL细胞的支持保护用从而治疗白血病提供新的策略。

急性淋巴细胞性白血病（ALL）是一种恶性血液病，大多数病人易复发及产生耐药，整体存活率低。许多证据表明骨髓微环境，如骨髓基质细胞（MSCs）对ALL细胞的保护作用有关。为明确保护机制，我们把ALL细胞与MSCs共培养，并从mRNA和蛋白水平检测了ALL细胞分子表达变化。结果表明，Wnt信号通路参与了MSCs介导的细胞耐药。阻滞Wnt信号通路可以提高ALL细胞对化疗药的敏感性，并延长ALL小鼠模型的生存期。靶向该通路,为白血病提供新的策略和治疗。