多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，约占所有造血系统恶性肿瘤的10%，病原生物感染所 致的慢性抗原刺激导致浆细胞转化可能是发病机制之一。申请人在前期工作中发现病原生物的识别受体-TOLL样受体在MM细胞中呈高表达，TLR4及TLR9的配体能够促进MM细胞增殖。基于上述结果我们猜测TLR4/9信号通路激活是促进MM细胞生长的机制之一。本课题拟通过检测不同疾病状态TLR4/9的表达水平,特异性干扰TLR4、9及TLR通路中关键接头蛋白MyD88的表达，进一步证实TLR4及9通路激活可以促进MM细胞生长；在动物模型中寻找TLR4/9促进MM细胞生长和免疫逃逸机制；并进一步通过激活和抑制下游信号通路、基因芯片及细胞因子分析等手段，寻找其TLR通路下游可能起主导作用的信号通路、分子及细胞因子。本课题预期研究结果可丰富MM发病机制，为寻找新的治疗靶点提供理论和实验基础。

Multiple myeloma (MM) arises from an accumulation of malignant plasma B cells in the bone marrow (BM), which accounts for about 10% of all hematological malignancies, however，the molecular mechanism of MM pathesenesis remains unclear.It was reported that plasma cells transformation, aberrant activation of signaling pathway and promotion of cytokines secretion might be responsible for the pathesenesis of MM. In our previous report we demonstrated that expression of Toll like receptor were higher in MM cells and TLR4 and TLR9 specific ligands could promote MM cells proliferation. Nevertheness, we hypothesized that activation of TLRs signaling pathway could promote MM cell growth.In this study, we want to confirm the expression of TLR4 ,TLR9 and other molecules downstream of TLR signaling pathway in MM patients and animal models, and specific interference of TLR4，TLR9 and the key adapt protein, MyD88, were further designed to verify the action of TLR signaling pathway on MM cell growth. In addition, sepecific inhibitor, microarray and cytokine analyse were employed to secreen the potential signaling molecules and search the dorminant cytokines. Take together, the expected results might enrich the molecular mechanism of MM pathesenesis and launch a solid basis of development of the new therapeutic targets.