摘要
目的研究程序性死亡配体1(PD-L1)在儿童初治急性髓系白血病(AML)中的表达及对白血病细胞耐药的影响。方法收集2020年1月至2021年1月郑州大学附属儿童医院血液肿瘤科收治的初诊40例AML病儿骨髓标本,收集同期进行骨髓检查正常病儿的骨髓标本18例作为正常对照组,比较两组骨髓中PD-L1的表达量,并分析初治AML病儿PD-L1的表达量与其临床特征之间的关系;慢病毒构建PD-L1过表达、干扰PD-L1表达的AML细胞,细胞活力检测试剂盒(CCK8)检测细胞增殖能力,并计算细胞对柔红霉素的药物敏感性;凋亡实验检测经柔红霉素诱导的细胞凋亡水平。结果与正常对照组0.887±0.064相比,初治儿童AML病儿骨髓单个核细胞PD-L1的表达量2.927±0.271显著增高(t=7.34,P<0.001);根据一个疗程诱导化疗是否达完全缓解(CR),将初治AML病儿一个疗程达CR者定义为CR组,将未达CR者定义为NR组,相较于CR组的2.346±0.190,NR组PD-L1基因的表达量5.249±0.662显著增高(t=4.22,P=0.003);病儿不同发病年龄,性别,法、美、英(FAB)分型,白细胞计数,预后分层间PD-L1基因相对表达量比较均差异无统计学意义(P>0.05),而1个疗程诱导化疗是否达CR与PD-L1基因相对表达量差异有统计学意义(P=0.018);过表达PD-L1的Molm-13细胞对柔红霉素具有更高的IC50值,更低的凋亡率;干扰PD-L1表达的THP1细胞对柔红霉素具有更低的IC50值,更高的凋亡率。结论PD-L1在初治AML病儿中表达增高,且PD-L1的高表达与1个疗程诱导治疗是否达CR显著相关;PD-L1可以促进AML细胞增殖、抑制凋亡,从而导致化疗耐药。
Objective To explore the expression of programmed death ligand 1(PD-L1)in childhood acute myeloid leukemia(AML)and its effect on leukemia cell resistance.Methods Bone marrow samples from 40 children with AML,who were admitted to the Department of Hematology and Oncology of the Children´s Hospital of Zhengzhou University from January 2020 to January 2021,were collected,and bone marrow samples from 18 normal children were collected as normal control groups.The expressions of PD-L1 in the bone marrow of the two groups were compared,and the relationship between the expression of PD-L1 and its clinical features in children with treatment-naïve AML was analyzed.AML cells that overexpressed and downregulated PD-L1 were constructed,and cell counting kit-8(CCK8)was used to detect cell proliferation for calculating the daunorubicin sensitivity.Apoptosis assays were used to measure daunorubicin-induced apoptosis levels.Results Compared with the normal control group,the gene expression of PD-L1 in bone marrow mononuclear cells of treatment-naïve AML group was significantly increased(0.887±0.064 vs.2.927±0.271;t=7.34,P<0.001).According to whether a course of induction chemotherapy achieved complete remission(CR),children with treatment-naïve AML who achieved CR after one course were defined as CR group,and those who did not achieve CR were defined as NR group.Compared with the CR group,the expression of PD-L1 in the NR group was significantly increased(2.346±0.190 vs.5.249±0.662;t=4.22,P=0.003).There was no significant difference in the relative expression of PD-L1 between different age of onset,gender,French-American-British(FAB)classification,white blood cell count,and prognosis stratification(P>0.05),while there were significant differences in CR after one course of induction chemotherapy and relative expression of PD-L1(P=0.018).Molm-13 cells overexpressing PD-L1 had higher IC50 values and lower apoptosis rates after treatment with daunorubicin;THP1 cells interfering with PD-L1 expression had lower IC50 values and higher apoptosis rates after treatment with daunorubicin.Conclusions The expression of PD-L1 is increased in children with treatment-naïve AML,and the high expression of PD-L1 is significantly related to whether CR is achieved after one course of induction chemotherapy.PD-L1 can promote proliferation and inhibit apoptosis of AML cells,thus resulting in drug resistance in chemotherapy.
作者
马平
田亮
周建文
毛彦娜
栗春香
何永艳
王亚峰
平玉豪
刘炜
MA Ping;TIAN Liang;ZHOU Jianwen;MAO Yanna;LI Chunxiang;HE Yongyan;WANG Yafeng;PING Yuhao;LIU Wei(Deparment of Hematology and Oncology,Children´s Hospital Affiliated to Zhengzhou University,Zhengzhou,He´nan 450000,China;Clinical College,Sanquan College,Xinxiang Medical College,Xinxiang,He´nan 453300,China)
出处
《安徽医药》
CAS
2024年第7期1446-1450,共5页
Anhui Medical and Pharmaceutical Journal
基金
河南省科技攻关项目(212102310036)。
关键词
白血病
髓样
急性
程序性死亡配体1
儿童
化疗耐药
柔红霉素
Leukemia,myeloid,acute
Programmed death ligand 1
Children
Chemotherapy resistance
Daunorubicin
