PD-L1在急性髓系白血病中的表达  

The Expression of PD⁃L1 in Acute Myeloid Leukemia

作　　者：杜晨霄 彭岚 肖湘遥 马金玉 滕广帅[1] 张宇卉 王艳 段依璠 邵宗鸿 白洁 DU Chen-xiao;PENG Lan;XIAO Xiang-yao;MA Jin-yu;TENG Guang-shuai;ZHANG Yu-hui;WANG Yan;DUAN Yi-fan;SHAO Zong-hong;BAI Jie(Department of Hematology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院血液科,天津300211

出　　处：《中国生物工程杂志》2023年第12期69-77,共9页China Biotechnology

基　　金：国家自然科学基金(82270148);天津市教委科研计划(2022ZD072、2022KJ253)资助项目。

摘　　要：目的:探讨程序性死亡分子1配体-1(programmed death 1 ligand 1,PD-L1)表达水平在急性髓系白血病发生及转化过程、治疗中的临床意义。方法:(1)利用GEO软件和GEO2R计算方法,以P<0.05、|logFC|>1为条件,分析公共数据库常见免疫检查点的表达情况;使用TCGA-LAML队列数据,利用Survival R包进行高表达PD-L1患者生存分析。(2)选取2017年10月至2023年3月在天津医科大学第二医院血液科确诊为急性髓系白血病的初治患者验证该结论,流式细胞术检测治疗前骨髓T细胞程序性死亡受体1(programmed cell death protein 1,PD-1)、CD34+原始细胞中PD-L1的表达水平,分析PD-1及PD-L1表达水平与患者临床特征、疗效及生存的相关性。结果:(1)急性髓系白血病(acute myeloid leukemia,AML)初诊患者中免疫检查点淋巴细胞活化基因3(lymphocyte lctivation gene 3,LAG3)、PD-1、PD-L1和T细胞免疫球蛋白黏蛋白分子3(T cell immunoglobulin domain and mucin domain-3,TIM3)表达较正常人高(P<0.05),初诊时PD-L1低表达组生存率高。(2)复发难治AML、继发性AML初诊时PD-L1表达水平更高,初诊AML患者PD-L1的高表达有复杂染色体核型、预后更差及生存更短的趋势。结论:PD-1/PD-L1信号通路可能参与髓系肿瘤细胞的免疫逃逸机制,其表达水平高与疾病恶性程度、进展呈正相关,与疗效和生存期呈负相关。Objective:To investigate the clinical significance of the expression level of programmed death molecule 1 ligand 1(PD⁃L1)in the occurrence,transformation,and treatment of acute myeloid leukemia(AML).Methods:First,using GEO software and GEO2R calculation method,with P<0.05 and|logFC|>1 as conditions,we analyzed the expression of common immune monitoring points in public databases.The data were analyzed using TCGA⁃LAML queue data and survival R packets for high expression PD⁃L1 patients.Second,we selected newly diagnosed AML patients in our department from October 2017 to March 2023 to verify our hypothesis.Flow cytometry was used to detect the expression levels of PD⁃L1 in the bone marrow T lymphocyte programmed cell death receptor 1(PD⁃1)and CD34+progenitor cells before treatment.The correlation between PD⁃1 and PD⁃L1 expression levels and patient clinical characteristics,efficacy,and survival was analyzed.Results:The expression of lymphocyte activation gene 3(LAG3),PD⁃1,PD⁃L1,and T cell immunoglobulin domain and mucin domain⁃3(TIM3)at immune checkpoint in the initially diagnosed AML patients was higher than that in normal individuals(P<0.05),and the survival rate was higher in the group with low PD⁃L1 expression at initial diagnosis.Recurrent and refractory AML and secondary AML have higher levels of PD⁃L1 expression at initial diagnosis.The high expression of PD⁃L1 in newly diagnosed AML patients tends to have complex chromosomal karyotypes,poorer prognosis,and shorter survival.Conclusions:The PD⁃1/PD⁃L1 signaling pathway may be involved in the immune escape mechanism of myeloid tumor cells,and its expression level is positively correlated with the malignancy and progression of the disease,while negatively correlated with treatment efficacy and survival.

关 键 词：程序性死亡分子1配体-1 髓系肿瘤 免疫逃逸 免疫治疗 

分 类 号：Q354[生物学—遗传学]