低剂量辐射及CD44单克隆抗体IM7对慢性髓细胞白血病干祖细胞辐射敏感性及归巢影响的实验分析-内科血液学专业论文.docx

IV IV 中文摘要 低剂量辐射及 CD44 单克隆抗体 IM7 对慢性髓细胞白血病干祖细胞辐射敏感性及归巢影响的实验研究 基因，从而促进 CML-CD34+细胞凋亡 （3）CD44 单抗 IM7 在体外能有效抑制 CML-CD34+细胞的粘附和迁移，从而为 白血病的靶向治疗提供新的治疗靶点与理论依据。 （4）CD44 单抗 IM7 能有效诱导 CML-CD34+细胞凋亡，可能机制为 IM7 与细胞 膜上 CD44 粘附分子受体结合后启动一系列异常信号通路，抑制了核转录因子 NF-κB 的活性，C-myc 及 Bcl-2 作为 NF-κB 下游效应靶基因表达下调，从而诱导 CML-CD34+ 细胞的凋亡。 综上所述：本研究表明（1）CML-CD34+细胞及脐血 CD34+细胞对射线均较敏感， 但两者之间的辐射敏感性的差异，可能与其细胞周期时相分布有关；（2）低剂量辐射 可特异性引发 CML-CD34+细胞的辐射兴奋效应，DNA 辐射损伤通过非 p53 依赖途径 诱导激活 p16 基因、DAPK1 基因，从而促进 CML-CD34+细胞凋亡；（3）抗 CD44 单 抗 IM7 在体外不仅能有效抑制 CML-CD34+细胞的粘附和迁移，而且还可以诱导 CML-CD34+细胞凋亡。研究结果提示 LDR 能特异性诱导白血病干祖细胞的辐射兴奋 效应、超敏感性，具有一定的抗肿瘤效应，该技术有一定的临床应用价值与潜力；IM7 对白血病干祖细胞归巢与粘附能力的影响，可为白血病干细胞靶向治疗富集新的治疗 策略与思路。 关键词：慢性粒细胞白血病；放射敏感性；细胞迁移；细胞粘附；细胞凋亡；低 剂量辐射；NF-κB；P16；DAPK1. 作 者：章龙珍 指导老师：陈子兴 教授 V V 低剂量辐射及 CD44 单克隆抗体 IM7 对慢性髓细胞白血病干祖细胞辐射敏感性及归巢影响的实验研究 英文摘要 The effects of LDR and IM7 on radiosensitivity and homing process of chronic myelogenous leukemia stem/progenitor cells and their mechanism Abstract 【Objects】 The LSCs ( leukemic stem cells ) are the major source of leukemic relapse, since 95% of these cells in the G0 phase, are not sensitive to conventional radiotherapy and chemotherapy. Development of novel therapeutic straties is greatly needed to eliminate LSCs, including the targeting therapy for LSCs, in combination with other treatment to improve the efficacy of targeted therapy. LSCs require the interaction with the niche to maintain their stem cell properties which provides therapeutic opportunity to block its selectively homing and engraftment. CD44 has been reported to play an important role in the process of tumor initiating. Krause’studies showed that CD44 had a key role in homing and engraftment of BCR-ABL-expressing leukemia stem cells. Most Leukemic stem cells keep in resting stage, being resistant to conventional radiation dose, whereas the non-conventional radiation dose became a research focus. The low-dose irradiation has been widely and intensively investigated due to its biological effects of adaptive re