抗CD44单抗IM7对慢性粒细胞白血病CD34^＋细胞黏附和迁移能力影响的体外研究  

In vitro effects of anti-CD44 monoclonal antibody on the adhesion and migration of chronic myeloid leukemia stem cells

作　　者：章龙珍[1] 丁昕[2] 李向阳[2] 岑建农[1] 陈子兴[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,215006 [2]徐州医学院附属医院放疗科

出　　处：《中华血液学杂志》2010年第6期398-402,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（30470733、30770916）

摘　　要：目的 探讨抗CD44单抗IM7在体外对慢性粒细胞白血病（CML）干细胞（LSC）黏附和迁移的影响及其机制.方法 取20例初诊CML患者骨髓及20名健康新生儿脐血标本,用免疫磁珠分离法分离纯化CML患者骨髓和正常人脐血CD34^＋细胞,流式细胞术检测CD123和CD44的表达情况,MTT法检测CD44单抗IM7孵育前后细胞的黏附能力,体外跨内皮迁移实验检测其迁移能力.结果 ①CML患者骨髓CD34^＋细胞（CML-CD34^＋细胞）中CD34和CD123双阳性细胞率为7.5%,CD44阳性细胞率为（86.60±2.10）%;脐血CD34^＋细胞中CD44阳性细胞率为（25.40±1.70）%,两组之间比较差异有统计学意义（P〈0.05）.②与IM7孵育后的CML-CD34^＋细胞与血管内皮细胞黏附能力为0.34±0.07[吸光度（A）570值],未经IM7处理组为0.62 ±0.11,CML-CD34^＋细胞经IM7处理后的黏附能力显著下降,而脐血CD34^＋细胞IM7处理前后无明显变化.③跨内皮迁移实验显示经IM7处理后的CML-CD34^＋迁移能力明显受到抑制,抑制率为46%～63%,而CD34^＋细胞迁移抑制不明显.④经IM7处理后的CML-CD34^＋细胞与骨髓基质细胞黏附能力明显降低,而脐血CD34^＋细胞IM7处理前后无明显变化.结论 CML患者来源的CD34^＋细胞与脐血CD34^＋细胞为性质不同的造血干细胞,抗CD44单抗IM7在体外能有效抑制CML-CD34^＋的黏附和迁移,从而为白血病的靶向治疗提供依据.Objective To explore the effects of anti-CD44 monoclonal antibody-IM7 on the in vitro adhesion and migration of chronic myeloid leukemia stem cell（CML-LSC） and its mechanism. Methods CD34＋ CD38- CD123＋ leukemic stem cells （LSC） from 20 newly-diagnosed chronic myeloid leukemia （ CML） patients BM cells and CD34＋ CD38- hematopoietic stem cells （HSC） from 20 full-term newborn cord blood cells were isolated with EasySepTM magnet beads. The CD44 expression of the LSC and HSC was detected by flow cytometry （FCM）, and the adhesion and migration ability of the LSC and HSC pre- and post-incubated with IM7 in vitro by MTT assay and transendothelial migration assay, respectively. Results ①After incubated with IM7, the LSC and HSC CD44 expression rates were （86.60±2.10）% vs. （25.40±1.70）% （P〈0.05）, respectively. ②The adhesive ability of the LSC to endothelial cells was decreased markedly after incubated with IM7, the OD value （A570） changing from pre- incubation of （0.62±0.11） to post-incubation of （0.34±0.07）, while there was little change of A570 in the HSC group. ③The migration abilityof the LSC group was inhibited evidently after incubated with IM7, the inhibition rate being 46%～63%, while little change of that in HSC group was detected. ④The adhesive ability of the LSC group to marrow stromal cells was decreased markedly after incubated with IM7, while little change was found in that of HSC group. Conclusion The anti-CD44 monoclonal antibody-IM7 can effectively inhibit the adhesion and migration abilities of the LSC in vitro, which might provide a theoretical evidence for targeting therapy.

关 键 词：白血病 髓样 慢性 抗体 CD44 细胞迁移 细胞黏附 

分 类 号：R733.72[医药卫生—肿瘤]