多发性骨髓瘤系浆细胞恶性克隆性疾病，目前发病率逐年增高且仍不可治愈。从浆细胞分化和存活调控入手，探索多发性骨髓瘤治疗的新靶点和新策略是一可行手段。Blimp-1是调控浆细胞分化和存活的关键转录因子，但对其在多发性骨髓瘤中的作用尚少有涉及。本课题组前期研究显示，骨髓瘤细胞高表达Blimp-1，RNA干扰沉默Blimp-1表达可通过抑制未折叠蛋白反应（unfolded protein response，UPR）破坏内质网稳态抑制骨髓瘤细胞增殖并诱导其凋亡。本研究拟在前期工作基础上通过基因敲除小鼠模型、骨髓瘤细胞株和原代细胞进一步研究Blimp-1调控UPR反应影响内质网稳态的作用及其对骨髓瘤发病的调控作用；并从转录调控和信号转导水平深入揭示Blimp-1调控骨髓瘤细胞的机制。课题如期完成有助于加深对骨髓瘤发病机制的理解，也能为多发性骨髓瘤防治提供新的潜在靶点和策略。

Multiple myeloma (MM) is a currently incurable plasma malignancy and the incidence goes up annually. There is one of feasible methods to explore new targets and strategy for the treatment of MM from the regulation of differentiation and survival of plasma cells. Blimp-1 is the key transcription factor to regulate differentiation and survival of plasma cells, but very little involved in MM. Our previous research has shown that myeloma cells highly expressed Blimp-1 and RNA interference silencing Blimp-1 expression damaged endoplasmic reticulum steady-state, inhibited myeloma cells proliferation and induced its apoptosis by inhibition of the UPR (unfolded protein response). Based on the previous work, the further study will focus on the influence of endoplasmic reticulum homeostasis and the pathogenesis of myeloma through regulating UPR reaction by Blimp-1 and deeply reveal the mechanism of Blimp-1 regulating myeloma cells from the transcription and signal transduction level using Blimp-1 knockout mice model, myeloma cell lines and primary cells. The project deadline helps to deepen the understanding of the pathogenesis of MM, and also can offer new potential targets and strategy for prevention and control of MM.