骨髓增生异常综合征患者低甲基化药物耐药的机制及其对策  

Mechanism and Its Countermeasure of Hypomethylating Agent Resistance in Patients with Myelodysplastic Syndrome-Review

作　　者：庞艳彬[1] 范丽霞[1] 薛华[1] 柳嘉[1] 杜欣 化罗明[1] 王静[1] PANG Yan-Bin;FANLi-Xia;XUE Hua;LIU Jia;DU Xin;HUA LuoMing;WANG Jing(Department of Hematology,The Afilliatied Hospital of Hebei Universtity,Bao/ing 01100,Hebei Province,China;Department of He-matology,Guangdong Peopled Hospital/Guangdong Academy of Meeiccl Sciences,the Mediccl ScCool qf Soutt China University qf Technology,Guangzhou 510080,Guangdong Province,China)

机构地区：[1]河北大学附属医院血液内科,河北保定071000 [2]广东省人民医院/广东省医学科学院,华南理工大学医学院血液内科,广东广州510080

出　　处：《中国实验血液学杂志》2018年第5期1574-1578,共5页Journal of Experimental Hematology

摘　　要：目前低甲基化药物(HMA)广泛用于骨髓增生异常综合征(MDS)的治疗,显著改善患者的临床治疗效果,但耐药现象几乎普遍存在。本文重点阐述HMA的免疫机制以及去甲基化治疗后免疫检查点受体表达上调是形成继发耐药的潜在机制。加深对ICP在HMA耐药机制中的认识,为在MDS中引入免疫检查点阻滞治疗(CBT)提供理论基础。免疫检查点通路(ICP)在HMA耐药中的作用有待进一步研究。CBT已是多种实体肿瘤的既定治疗方案,在部分血液肿瘤中也具有辅助治疗作用。CBT在MDS中的适宜性和有效性有待正在进行的临床试验结果予以证实。Hypomethylating agents(HMA)currently are widely used in the treatment of myelodysplastic syndromes(MDS),provide a significant improvement in the treatment of MDS.However,resistance to HMA is an almost universal phenomenon.This review was focused on immune effects related to DNA methylation,and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways.However,the optimal role of checkpoint blockade therapy(CBT)and immune checkpoint pathways remain in HMA failure questionable.The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBTin patients as a novel treatment option.CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies,therefore,may alter the treatment landscape in MDS.The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials,so as to find novel strategies to improve outcome after failure of HMA.

关 键 词：骨髓增生异常综合征 免疫检查点 耐药 低甲基化药物 

分 类 号：R557.1[医药卫生—血液循环系统疾病]