免疫标记物CCR7在慢性淋巴细胞白血病和其他慢性B淋巴细胞增殖性疾病中的诊断和鉴别诊断价值  

Diagnosis and differential diagnosis value of immune marker CCR7 in chronic lymphocytic leukemia and other chronic B-cell lymphoproliferative disorders

作　　者：刘露[1] 赵四书 陈肖 乔纯[1] 仇海荣[1] 王琰[1] 郭睿[1] 李建勇[1] 吴雨洁[1] Liu Lu;Zhao Sishu;Chen Xiao;Qiao Chun;Qiu Hairong;Wang Yan;Guo Rui;Li Jianyong;Wu Yujie(Department of Hematology,the First Affiliated Hospital of Nanjing Medical University(Jiangsu Provincial Hospital),Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院(江苏省人民医院)血液科,南京210029

出　　处：《中华检验医学杂志》2022年第11期1155-1162,共8页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(81370656)。

摘　　要：目的探讨免疫标记物CC-趋化因子受体7(CCR7)抗原在慢性淋巴细胞白血病(CLL)诊断和鉴别诊断中的价值。方法收集南京医科大学第一附属医院2015年1月至2018年12月间收治的B型慢性淋巴细胞增殖性疾病(B-CLPD)患者643例,包括327例CLL、58例套细胞淋巴瘤(MCL)、34例滤泡淋巴瘤(FL)、36例边缘区淋巴瘤(MZL)、10例毛细胞白血病或其变异型(HCL/HCL-v)、40例华氏巨球蛋白血症(WM),以及48例CD5+B型慢性淋巴细胞增殖性疾病未分类(B-CLPD-U)和90例CD5-B-CLPD-U。同时收集本院健康管理中心2018年20名正常对照样本。利用流式细胞术检测B-CLPD患者免疫表型及CCR7表达,采用荧光原位杂交技术(FISH)分析了共济失调毛细血管扩张突变基因(ATM)缺失、13q14缺失、P53缺失和12三体,并利用Sanger测序分析了剪接因子3b亚基1(SF3B1)、NOTCH1、肿瘤蛋白53(TP53)和免疫球蛋白重链可变区(IGHV)的基因突变情况。计量资料的比较采用Mann-Whitney检验,率的比较采用χ^(2)检验。CCR7的诊断价值和最佳阳性界值利用受试者工作特征(ROC)曲线计算。结果CCR7在典型CLL和非典型CLL中阳性表达率分别为90.8%(257/283)和84.1%(37/44),阳性率差异无统计学意义(χ^(2)=1.228,P=0.268)。CCR7在CLL中阳性表达率为89.9%(294/327),平均荧光强度(MFI)为278(246,307),而CCR7在MCL、CD5+B-CLPD、CD5-B-CLPD、FL、WM、HCL/HCL-v和MZL中的阳性表达率分别为10.3%(6/58)、6.3%(3/48)、8.9%(8/90)、0、0、0和13.9%(5/36),MFI分别为114(106,128)、112(106,117)、110(104,121)、108(105,119)、111(105,124)、112(108,115)和109(105,120),与CLL相比,其他类型B-CLPD中CCR7阳性表达率较低,差异具有统计学意义(χ^(2)=181.3、177.8、232、164.7、180.8、62.6、129,P<0.01)。另外CCR7阳性用于鉴别CLL与其他类型B-CLPD的敏感度、特异度和准确度分别为89.9%、93.0%和92.3%。CCR7+CLL患者CD49d阳性表达率为13.9%,低于CCR7-CLL患者(42.1%)(χ^(2)=7.6,P=0.01);而13q14缺失发�Objective To investigate the clinical significance of cc-chemokine receptor 7(CCR7)as a potential diagnostic or differential marker for chronic lymphocytic leukemia(CLL).Methods A total number of 643 patients with B-cell chronic lymphoproliferative diseases(B-CLPD)admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled.The patients included 327 cases of CLL,58 cases of mantle cell lymphoma(MCL),34 cases of follicular lymphoma(FL),36 cases of marginal zone lymphoma(MZL),10 cases of hair-cell leukemia or its variants(HCL/HCLV-v),40 cases of Waldorf′s macroglobulinemia(WM),48 cases of CD5+B-cell chronic lymphoproliferative disease unclassified(B-CLPD-U)and 90 cases of CD5-B-CLPD-U.At the same time,20 samples from healthy people from the medical examination center of our hospital were used as normal controls.Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients,and Fluorescence in situ hybridization(FISH)was used to analyze the genomic alterations:the ataxia telangiectasia mutant gene(ATM)deletion,the 13q14 deletion,the P53 deletion and trisomy 12.Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1(SF3B1),NOTCH1,tumor protein 53(TP53)and immunoglobulin heavy chain variable region(IGHV).Measurement data were compared by Mann-Whitney test,and the positive rates were compared by chi-square test.The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic(ROC)curve.Results The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8%(257/283)and 84.1%(37/44),respectively,and there was no significant difference of the positive rates(χ^(2)=1.228,P=0.268)between groups.The positive expression rates of CCR7 in CLL,MCL,CD5+B-CLPD-U,CD5-B-CLPD-U,FL,WM,HCL/HCL-v and MZL were 89.9%(294/327),10.3%(6/58),6.3%(3/48),8.9%(8/90),0,0,0 and 13.9%(5/36)respectively,and the median mean fluorescence intensity(MFI)was 2

关 键 词：受体 趋化因子 淋巴瘤 流式细胞术 

分 类 号：R733[医药卫生—肿瘤] R730.43[医药卫生—临床医学]