BCR-ABL抑制剂的皮肤不良反应及其发生机制研究进展  

Research Progress of Cutaneous Adverse Reactions and Mechanism of BCR-ABL Inhibitors

作　　者：胡泰然 闫言 王宝玺 HU Tairan;YAN Yan;WANG Baoxi(Department of Dermatology,Plastic Surgery Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100144,China)

机构地区：[1]中国医学科学院北京协和医学院整形外科医院皮肤科,北京100144

出　　处：《医学综述》2021年第22期4475-4480,共6页Medical Recapitulate

基　　金：国家自然科学基金(82073471)。

摘　　要：以断裂点簇集区(BCR)-艾贝尔逊白血病病毒(ABL)蛋白为靶点的酪氨酸激酶抑制剂是费城染色体阳性白血病患者的靶向治疗药物,但存在许多皮肤不良反应,其中部分不良反应可能与BCR蛋白的功能失调有关。BCR基因位于第22号染色体长臂,参与费城染色体中BCR-ABL融合基因的产生。BCR基因编码的蛋白质具有独特结构,含有多个功能不同的结构域并调节不同的生理活动,其N端结构域具有丝氨酸/苏氨酸激酶活性,中央结构域可激活小鸟苷三磷酸(GTP)结合蛋白,C端结构域可使小GTP结合蛋白失活。因此,未来深入研究BCR基因和BCR蛋白的功能,有助于从机制上进一步认识并预防BCR-ABL抑制剂的皮肤不良反应。Tyrosine kinase inhibitors targeting breakpoint cluster region(BCR)-Abelson leukemia virus(ABL)protein are targeted therapies for Philadelphia chromosome positive leukemia.However,cutaneous adverse reactions often occur in the application,and some of the adverse reactions may be related to the dysfunction of BCR protein.BCR gene is located in the long arm of chromosome 22,which is involved in the production of BCR-ABL fusion gene in Philadelphia chromosome.The protein encoded by BCR gene has a unique structure,which contains multiple functional domains and regulates different physiological activities:the N-terminal domain has serine/threonine kinase activity;the central domain activates small guanosine triphosphate(GTP)-binding proteins,while the C-terminal domain inactivates them.Therefore,exploring the function of BCR gene and BCR protein is helpful to further understand and prevent these cutaneous adverse reactions of BCR-ABL inhibitors from the mechanism in the future.

关 键 词：皮肤不良反应 断裂点簇集区 艾贝尔逊白血病病毒 功能结构域 费城染色体 酪氨酸激酶抑制剂 

分 类 号：R758.6[医药卫生—皮肤病学与性病学]