细胞周期蛋白依赖性激酶4/6抑制剂对多发性骨髓瘤细胞B细胞成熟抗原和程序性死亡受体配体1表达的影响  

Effects of cyclin-dependent kinase 4/6 inhibitors on B-cell maturation antigen and programmed death-ligand 1 in myeloma cells

作　　者：谢适意 于珍 魏晓晶 邹鹤松 张悦 邱录贵 徐燕 XIE Shiyi;YU Zhen;WEI Xiaojing;ZOU Hesong;ZHANG Yue;QIU Lugui;XU Yan(State Key Laboratory of Erperimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Department of Hematology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China;Department of Hematology,Zhengzhou People's Hospital,People's Hospital of Henan University of Chinese Medicine,Zhengzhou,Henan 450053,China)

机构地区：[1]中国医学科学院,北京协和医学院血液病医院(中国医学科学院血液学研究所),血液与健康全国重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津医学健康研究院,天津300020 [2]天津医科大学第二医院血液内科,天津300211 [3]郑州人民医院,河南中医药大学人民医院血液内科,河南郑州450053

出　　处：《中华实用诊断与治疗杂志》2024年第6期546-551,共6页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金(82170203);河南省科技攻关计划项目(212102310786)。

摘　　要：目的 探讨细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂对多发性骨髓瘤(MM)细胞免疫治疗相关分子B细胞成熟抗原(BCMA)、程序性死亡受体配体1(PD-L1)表达及MM细胞和正常微环境细胞凋亡的影响。方法 对数生长期H929细胞分为阿贝西利组、帕博西尼组、DMSO组,于细胞培养基中分别加入2μmol/L阿贝西利、5μmol/L帕博西尼和等体积DMSO处理,处理1、3、5 d时,采用流式细胞术检测3组细胞BCMA、PD-L1相对平均荧光强度。2020年1月—2023年6月中国医学科学院血液病医院诊治MM患者3例,采集患者骨髓,采用淋巴细胞分离液分离骨髓单个核细胞,分为阿贝西利组、帕博西尼组、DMSO组,分别给予1μmol/L阿贝西利、10μmol/L帕博西尼和等体积DMSO处理,采用流式细胞术检测CD138+肿瘤细胞和CD138-正常微环境细胞相对细胞存活率。结果 帕博西尼组处理1、3、5 d时BCMA相对平均荧光强度(1.37±0.04、2.36±0.11、3.99±0.17)均高于阿贝西利组(0.69±0.02、1.03±0.05、1.69±0.06)(P<0.05),处理3、5 d时均高于DMSO组(1.00±0.02、1.00±0.05)(P<0.05),处理1 d时与DMSO组比较差异无统计学意义(P>0.05);阿贝西利组处理5 d时BCMA相对平均荧光强度高于DMSO组(P<0.05),处理1、3 d时与DMSO组比较差异均无统计学意义(P>0.05);阿贝西利组、帕博西尼组处理1、3、5 d时BCMA相对平均荧光强度均依次增高(P<0.05)。处理1、3、5 d时,阿贝西利组、帕博西尼组PD-L1相对平均荧光强度(1.30±0.02、3.21±0.10、2.28±0.17,1.28±0.12、2.81±0.38、2.00±0.16)均高于DMSO组(1.00±0.09、1.00±0.06、1.00±0.14)(P<0.05),阿贝西利组与帕博西尼组比较差异均无统计学意义(P>0.05);阿贝西利组、帕博西尼组处理3 d时均高于处理1、5 d时(P<0.05),处理5 d时高于处理1 d时(P<0.05)。处理24、48 h时,阿贝西利组、帕博西尼组骨髓单个核细胞CD138+相对细胞存活率均低于DMSO组(P<0.05),帕博西尼组均低于阿贝西利组(P<0.05Objective To investigate the influences of cyclin-dependent kinase 4/6(CDK4/6)inhibitors on the expressions of multiple myeloma(MM)cellular immunotherapy-associated molecules B-cell maturation antigen(BCMA)and programmed death-ligand 1(PD-L1)and on the apoptosis of MM cells and cells in normal microenvironment.Methods H929 cells in logarithmic growth phase were divided into abemaciclib,palbociclib and DMSO groups,and treated with 2μmol/L abemaciclib,5μmol/L palbociclib and equivalent volume of DMSO in cell culture medium,respectively.The relative mean fluorescence intensities of BCMA and PD-L1 were detected by flow cytometry on day 1,3 and 5 of culture in three groups.The bone marrow was collected from 3 MM patients diagnosed and treated in Blood Diseases Hospital of Chinese Academy of Medical Sciences from January,2020 to June,2023,and the bone marrow mononuclear cells were separated by using lymphocyte isolation solution,and divided into abemaciclib,palbociclib and DMSO groups,which were treated with 1μmol/L abemaciclib,10μmol/L palbociclib,and equivalent volume of DMSO respectively.Flow cytometry was used to detect the relative cell survival rates of CD138^(+)tumor cells and GD138 cells in normal microenvironment.Results The relative mean fluorescence intensities of BCMA were higher in palbociclib group(1.37±0.04,2.36±0.11,3.99±0.17)than those in abemaciclib group(0.69±0.02,1.03±0.05,1.69±0.06)on day 1,3 and 5 of culture(P<0.05),and were higher in palbociclib group than those in DMSO group(1.00±0.02,1.00±0.05)on day 3 and 5(P<0.05),while there was no significant difference between palbociclib group and DMSO group on day 1(P>0.05),In abemaciclib group,the relative mean fluorescence intensity of BCMA was higher than that in DMSO group on day 5(P<0.05),and showed no significant difference on day 1 and 3compared with DMSO group(P>0.05).The relative mean fluorescence intensities of BCMA increased sequentially in abemaciclib group and palbociclib group on day 1,3 and 5(P<0.05).On day 1,3 and 5,the relati

关 键 词：多发性骨髓瘤 细胞周期蛋白依赖性激酶4/6 阿贝西利 帕博西尼 B细胞成熟抗原 程序性死亡受体配体1 

分 类 号：R733.3[医药卫生—肿瘤]