MSC通过CXCL12/CXCR4轴介导CML细胞对TKI耐药的研究进展  

Research Progress on TKI Resistance of CML Cells Mediated by MSC through CXCL12/CXCR4 Axis——Review

作　　者：房丽君[1,2,3] 涂怀军[4] 李剑[1] 

机构地区：[1]南昌大学第二附属医院血液重点实验室,江西南昌330006 [2]南昌大学第二附属医院 [3]南昌大学研究生院医学部,江西南昌330006 [4]南昌大学第二附属医院神经内科,江西南昌330006

出　　处：《中国实验血液学杂志》2015年第4期1221-1224,共4页Journal of Experimental Hematology

基　　金：江西省主要学科学术和技术带头人培养对象项目;江西省重大基础研究项目(20143ACB20005)资助

摘　　要：酪氨酸激酶抑制剂(TKI)治疗慢性粒细胞性白血病(CML)的效果虽然显著,但其治疗过程中产生的耐药问题仍无法避免。最近研究表明,间充质干细胞(MSC)可以通过调节CXCL12/CXCR4轴来影响CML细胞定向性迁移、黏附至骨髓腔,介导CML细胞的保护性休眠、活化众多促存活通路、抑制线粒体介导的CML细胞凋亡及通过上调抗凋亡基因BCL-6的表达介导耐药。TKI联合CXCR4抑制剂有望成为提高CML遗传学治愈的新的治疗策略。本文就MSC介导CML细胞耐药途径,MSC增强CML细胞对CXCL12敏感性的途径及MSC增强CML细胞对骨髓血管黏附的途径进行综述。Although the tyrosinekinase inhibitors( TKI) displayed a significant curative effect on chronic myeloid leukemia( CM L),but the drug resistance in treatment course of this disease still can not be avoided. Studies recently have shown that the mesenchymal stem cells( M SC) can induce CM L cells to resist TKI therapy by CXCL12 / CXCR4 axis from multiple aspects,such as the directional migration of CM L cells,adherence to marrowcavity,the mediation of cell protective dormancy, activations of numerous survival signaling pathways, the suppression of mitochondrialdependent apoptosis and the up-regulated expression of BCL-6. The combination of TKI and CXCR4 antagonists will be a novel treatment strategy to raise the genetic cure rate of CM L. In this article,the pathways of drug resistance,pathways of sensitivity to CXCL12 and pathways of CM L cell adherence to marrowcavity in CM L cells mediated by M SC were reviewed.

关 键 词：间充质干细胞 慢性粒细胞性白血病 酪氨酸激酶抑制剂 CXCL12/CXCR4轴 耐药 

分 类 号：R733.7[医药卫生—肿瘤]