Fang Li-Jun, Tu Huai-Jun, Li Jian
Key Laboratory of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
Medical Department of Nanchang University Graduate School, Nanchang 330006, Jiangxi Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Aug;23(4):1221-4. doi: 10.7534/j.issn.1009-2137.2015.04.062.
Although the tyrosinekinase inhibitors (TKI) displayed a significant curative effect on chronic myeloid leukemia (CML), but the drug resistance in treatment course of this disease still can not be avoided. Studies recently have shown that the mesenchymal stem cells (MSC) can induce CML cells to resist TKI therapy by CXCL12/CXCR4 axis from multiple aspects, such as the directional migration of CML cells, adherence to marrow cavity, the mediation of cell protective dormancy, activations of numerous survival signaling pathways, the suppression of mitochondrial-dependent 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 CML. In this article, the pathways of drug resistance, pathways of sensitivity to CXCL12 and pathways of CML cell adherence to marrow cavity in CML cells mediated by MSC were reviewed.
尽管酪氨酸激酶抑制剂(TKI)对慢性髓性白血病(CML)显示出显著的治疗效果,但该疾病治疗过程中的耐药性仍无法避免。最近的研究表明,间充质干细胞(MSC)可通过CXCL12/CXCR4轴从多个方面诱导CML细胞对TKI治疗产生耐药性,如CML细胞的定向迁移、对骨髓腔的黏附、细胞保护性休眠的介导、众多生存信号通路的激活、线粒体依赖性凋亡的抑制以及BCL-6表达的上调。TKI与CXCR4拮抗剂联合使用将是提高CML基因治愈率的一种新型治疗策略。本文综述了MSC介导的CML细胞中耐药途径、对CXCL12敏感途径以及CML细胞对骨髓腔黏附途径。