IL-9在多发性骨髓瘤患者中的表达及其临床意义

发布时间：2018-04-05 13:35

本文选题：多发性骨髓瘤　切入点：IL-9　出处：《山东大学》2017年硕士论文

【摘要】：研究背景:多发性骨髓瘤(Multiple myeloma,MM)是一种最常见的恶性程度很高的血液系统肿瘤,其特点是单克隆浆细胞的恶性增殖及聚集。尽管新的治疗方案如大剂量化疗,造血干细胞移植以及新药如蛋白酶体抑制剂的应用提高了 MM的完全缓解率,并使得患者的生存期有了显著提高,但是MM现在仍然不能治愈。目前研究发现骨髓微环境对骨髓瘤的发生发展中发挥重要作用,和正常的浆细胞一样,骨髓瘤细胞的增殖依赖于与骨髓基质细胞之间发生的相互作用和由这两类细胞分泌的多种重要的细胞因子,如IL-6、IL1-b、肿瘤坏死因子(TNF-α)、生长转化因子-β(TGF-β)、IL-17、IL-21、血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)等。白介素-9(IL-9)主要由T辅助细胞分泌,在细胞因子网络中可发挥重要作用。通过与其受体(IL-9R)发生特异性结合发挥生物学作用,该受体由两条链组成,其中特异性结合链为α链,γ链则同时参与IL-2、IL-7、IL-15、IL-17和IL-21等细胞因子介导的信号通路。除了在免疫及肺部炎症中的作用外,越来越多的研究发现IL-9是一种可促进肿瘤形成的细胞因子。在T细胞淋巴瘤,B细胞淋巴瘤,霍奇金淋巴瘤,髓系恶性肿瘤,慢性淋巴细胞白血病患者的病理组织活检及血清中均可检测到IL-9的表达上调。然而,到目前为止,IL-9在骨髓瘤中的致癌活性仍未见报道。研究目的:多发性骨髓瘤(MM)的治疗虽已取得了很大进展,但其分子生物学机制尚不清楚,制约了进一步发展。目前已有研究发现IL-9及其受体在某些血液系统恶性肿瘤中高表达并参与疾病的进展,但是在MM中未有相关报道。本课题的目的是通过探究MM患者外周血中IL-9的表达水平并追踪其与患者临床资料之间的联系,进一步了解IL-9在MM发生、发展中的作用。材料与方法:1.标本采集及临床资料采集2.外周血血清分离3.Elisa 分析4.统计分析结果与结论:1.MM患者血清IL-9水平与健康对照组相比显著增高(P0.0001)。2.MM患者血清IL-9水平与血红蛋白浓度呈负相关(r = 0.5850,P = 0.0108)。3.根据肌酐水平将初发初治MM患者分为肾功能损害组和肾功能正常组,结果发现前者血清IL-9显著高于后者(P = 0.0395)。4.我们的发现提示IL-9异常表达可能在MM肾病以及贫血的发生、发展方面起重要作用。此结论有待进一步研究证实。
[Abstract]:Background: multiple myeloma (MM) is one of the most common hematologic tumors with high malignancy, characterized by the malignant proliferation and aggregation of monoclonal plasmacytes.Although new treatments such as high-dose chemotherapy, hematopoietic stem cell transplantation and the use of new drugs such as proteasome inhibitors have improved the complete remission rate of MM and significantly improved the survival of patients, MM is still incurable.Recent studies have found that bone marrow microenvironment plays an important role in the development of myeloma, just like normal plasma cells.The proliferation of myeloma cells depends on the interaction with bone marrow stromal cells and the production of many important cytokines by these two types of cells.For example, IL-6, TNF- 伪, TGF- 尾, IL-17, VEGF, IGF-1, et al.Interleukin-9 (IL-9) is secreted by T-helper cells and plays an important role in cytokine networks.The receptor is composed of two chains, the specific binding chain is 伪 chain, and the 纬 chain is involved in the signaling pathway mediated by cytokines such as IL-7, IL-15, IL-17 and IL-21.In addition to its role in immune and pulmonary inflammation, more and more studies have found that IL-9 is a cytokine that promotes tumor formation.Upregulation of IL-9 expression was detected in T cell lymphoma, Hodgkin's lymphoma, myeloid malignancy and chronic lymphoblastic leukemia (CLL).However, the carcinogenic activity of IL-9 in myeloma has not been reported.Objective: although great progress has been made in the treatment of multiple myeloma (MMM), its molecular biological mechanism is still unclear, which restricts its further development.At present, it has been found that IL-9 and its receptors are highly expressed in some hematological malignancies and participate in the progression of the disease, but there is no related report in MM.The purpose of this study is to explore the expression of IL-9 in the peripheral blood of MM patients and to follow up the relationship between IL-9 and clinical data, and to further understand the role of IL-9 in the pathogenesis and development of MM.Materials and methods: 1.Specimen collection and clinical data collection.Analysis of 3.Elisa in peripheral blood serum.Results and conclusions: 1. The serum IL-9 level in MM patients was significantly higher than that in healthy controls (P 0.0001). 2.There was a negative correlation between serum IL-9 level and hemoglobin concentration in patients with MM (r = 0.5850U, P = 0.0108, P = 0.0108. 3).According to the level of creatinine, the newly diagnosed MM patients were divided into two groups: renal function impairment group and normal renal function group. The results showed that the serum IL-9 in the former group was significantly higher than that in the latter group (P = 0.0395. 4).Our findings suggest that abnormal expression of IL-9 may play an important role in the pathogenesis and development of MM nephropathy and anemia.This conclusion needs further study and confirmation.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.3

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