LMLN通过SHP-1/JAK2/STAT3信号通路调控多发性骨髓瘤耐药和转移的机制研究

多发性骨髓瘤是一种来源于浆细胞的血液系统恶性肿瘤。目前该疾病的治疗及预后情况均不理想，尤其是复发耐药和髓外浸润的患者治疗效果较差。越来越多的研究发现抑制性肿瘤免疫微环境和免疫逃逸是肿瘤复发耐药及侵袭转移的主要因素。本课题前期研究发现LMLN可抑制多发性骨髓瘤细胞的侵袭和迁移，mRNA测序发现LMLN可能调控酪氨酸磷酸酶SHP-1的表达，而SHP-1可去磷酸化JAK2进而抑制STAT3磷酸化，最终抑制STAT3相关的肿瘤增长、耐药和转移。我们结合前期发表的文章和预实验结果提出科学假说：LMLN通过SHP-1/JAK2/STAT3信号通路调控多发性骨髓瘤的免疫微环境，抑制侵袭迁移和免疫逃逸。本课题通过探究LMLN/SHP-1/JAK2/STAT3信号通路调控多发性骨髓瘤复发耐药和侵袭迁移的机制，为克服耐药和转移提供新的治疗思路及潜在靶点。

Multiple myeloma is a hematological malignancy derived from plasma cells. At present, the treatment and prognosis of the disease are not ideal, especially in patients with relapse, drug resistance and extramedullary infiltration. More and more studies have found that inhibitory tumor immune microenvironment and immune escape are the main factors of tumor recurrence, drug resistance, invasion and metastasis. Previous studies of this project found that LMLN can inhibit the invasion and migration of multiple myeloma cells. mRNA sequencing found that LMLN may regulate the expression of tyrosine phosphatase SHP-1, and SHP-1 can dephosphorylate JAK2 and then inhibit the phosphorylation of STAT3, and ultimately inhibit the growth, drug resistance and metastasis of STAT3 related tumors. Combined with previous published articles and preliminary experimental results, we proposed a scientific hypothesis: LMLN regulates the immune microenvironment of multiple myeloma through SHP-1 / JAK2 / STAT3 signaling pathway, and inhibits invasion, metastasis and immune escape. This project aims to explore the mechanism of LMLN / SHP-1 / JAK2 / STAT3 signaling pathway regulating relapse, drug resistance, invasion and migration of multiple myeloma, so as to provide new therapeutic ideas and potential targets for overcoming drug resistance and metastasis.