Flap核酸内切酶1在急性髓系白血病中的表达及其临床意义  

Expression and clinical significance of Flap endonuclease 1 in acute myeloid leukemia

作　　者：刘彦权 曾敏娟 殷悦[3] 陈玉婷 唐焕文 Liu Yanquan;Zeng Minjuan;Yin Yue;Chen Yuting;Tang Huanwen(Department of Hematology,the First School of Clinical Medicine,Guangdong Medical University,Dongguan 523808,China;Department of Anatomy,School of Basic Medicine,Guangdong Medical University,Dongguan 523808,China;Department of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,China;Dongguan Key Laboratory of Environmental Medicine,School of Public Health,Guangdong Medical University,Dongguan 523808,China)

机构地区：[1]广东医科大学第一临床医学院血液内科,东莞523808 [2]广东医科大学基础医学院解剖学教研室,东莞523808 [3]福建医科大学附属协和医院血液科,福州350001 [4]广东医科大学公共卫生学院东莞市环境医学重点实验室,东莞523808

出　　处：《肿瘤研究与临床》2023年第4期246-251,共6页Cancer Research and Clinic

基　　金：国家自然科学基金面上项目(82073582);广东省教育厅高校特色创新项目(2020KTSCX048);广东医科大学学科建设项目(4SG22003G、4SG21209G);广东医科大学科技创新专项计划(4SG22046G)。

摘　　要：目的:探讨Flap核酸内切酶1(FEN1)在急性髓系白血病(AML)患者骨髓单个核细胞中的表达水平及其与临床病理特征、疗效的关系,为AML患者病情监测与靶向治疗提供新方向。方法:回顾性分析广东医科大学第一临床医学院、福建医科大学附属协和医院2018年11月至2020年12月57例初治AML患者和26名健康人(健康对照)的资料。收集所有受试者骨髓标本,采用实时荧光定量聚合酶链反应(qRT-PCR)检测受试者骨髓单个核细胞FEN1 mRNA的表达水平;抽取9例初治AML患者和4名健康对照骨髓标本,采用蛋白质印迹法检测FEN1蛋白表达水平。比较有疗效评估资料的AML患者中不同疗效者FEN1 mRNA表达水平差异。以FEN1 mRNA中位相对表达量为临界值,将AML患者分为FEN1高表达组(≥临界值)和低表达组(<临界值),分析FEN1表达水平与AML患者初诊时临床病理特征、实验室指标、细胞及分子遗传学改变的关系。结果:初治AML患者FEN1 mRNA中位相对表达量高于健康对照[0.696(0.025~3.661)比0.246(0.013~1.237), Z=1.75, P=0.041]。蛋白质印迹法检测显示,AML患者的FEN1蛋白表达水平高于健康对照。复发AML患者(15例)FEN1 mRNA相对表达量高于完全缓解(CR)患者(19例)[1.153(0.047~4.172)比0.259(0.023~1.148), Z=2.71, P=0.009]。初诊时,FEN1高表达组(32例)患者临床法、美、英协作组(FAB)分型M 5、初诊时伴发热及淋巴结肿大患者比例均高于FEN1低表达组(25例)(均 P<0.05),两组间不同性别、年龄、疲劳、皮肤黏膜苍白及肝脾大患者比例差异均无统计学意义(均 P>0.05);FEN1高表达组患者初诊时白细胞计数、乳酸脱氢酶、C反应蛋白、骨髓原始细胞比例均高于FEN1低表达组(均 P<0.05),血红蛋白、血小板计数均低于FEN1低表达组(均 P<0.05),两组间降钙素原水平及染色体核型、细胞遗传学预后分级和是否基因突变患者比例差异均无统计学意义(均 P>0.05)。 结论:AML患者FEN1表�Objective To investigate the expression level of flap endonuclease 1(FEN1)in bone marrow mononuclear cells of patients with acute myeloid leukemia(AML)and its relationship with clinicopathologic features and therapeutic effect,so as to provide a new direction for disease monitoring and targeted therapy in AML patients.Methods The data of 57 newly treated AML patients and 26 healthy individuals(the healthy control)from the First Clinical College of Guangdong Medical University and Fujian Medical University Union Hospital from November 2018 to December 2020 were retrospectively analyzed.Bone marrow samples of all subjects were collected.Quantitative real-time fluorescence polymerase chain reaction(qRT-PCR)was used to detect FEN1 mRNA expression in bone marrow mononuclear cells of all subjects.Bone marrow samples from 9 newly-diagnosed AML patients and 4 healthy controls were collected,and FEN1 protein expression level was detected by using Western blotting.Differences in FEN1 mRNA expression in AML patients achieving different therapeutic effects were compared among AML patients whose data with evaluable efficacy.AML patients were divided into high FEN1 expression group(≥critical value)and low FEN1 expression group(<critical value),taking the median relative expression level of FEN1 mRNA as the critical value.The correlation of FEN1 expression level with clinicopathologic features,laboratory indicators,cellular and molecular genetic changes in AML patients at initial diagnosis was analyzed.Results The median relative expression of FEN1 mRNA in newly treated AML patients was higher than that in healthy controls[0.696(0.025-3.661)vs.0.246(0.013-1.237),Z=1.75,P=0.041].Western blotting showed that the expression level of FEN1 protein in AML patients was higher than that in healthy controls.The relative expression of FEN1 mRNA in 15 recurrent AML patients was higher than that in 19 patients patients achieving complete remission(CR)[1.153(0.047-4.172)vs.0.259(0.023-1.148),Z=2.71,P=0.009].The proportion of patients with

关 键 词：白血病 髓样 急性 DNA瓣核酸内切酶类 肿瘤标记 生物学 

分 类 号：R733.71[医药卫生—肿瘤]