白细胞分化抗原160对慢性淋巴细胞白血病的诊断及预后意义

Diagnostic and prognostic value of CD160 antigen in patients with chronic lymphocytic leukemia

目的探讨CD160抗原在慢性淋巴细胞白血病(CLL)中的表达及在临床诊断中的价值,以及CD160抗原表达与患者的遗传学异常的相关性.方法回顾性研究.收集2015年1月至2017年12月南京医科大学第一附属医院(江苏省人民医院)收治的初诊的成熟小B细胞淋巴瘤336例.依据2008年第4版《造血和淋巴组织肿瘤的WHO分类》诊断200例CLL患者,根据英国马斯登皇家医院免疫标志积分系统又分为典型CLL122例,其中男80例,女42例,年龄45~82岁(中位年龄65岁);不典型CLL78例,其中男48例,女30例,年龄43~76岁(中位年龄60岁);49例套细胞淋巴瘤(MCL)患者,其中男39例,女10例,年龄27~70岁(中位年龄56岁);以及87例CD5-的小B细胞淋巴瘤(SBL)患者,其中男60例,女27例,年龄38~80岁(中位年龄63岁).应用多参数流式细胞术(FCM)检测336例患者肿瘤细胞CD160的表达率和平均荧光强度(MFI),同时采用荧光原位杂交(FISH)技术检测145例CLL患者P53缺失、107例CLL患者13q14缺失、110例CLL患者ATM缺失、104例CLL患者6q23缺失、104例CLL患者+12,以及138例CLL患者IGH重排,比较CD160+CLL患者与CD160-CLL患者遗传学和分子生物学特点.结果122例典型CLL患者中CD160阳性表达率为59.8%(73/122),MFI范围为14.9~173.9,78例不典型CLL患者中CD160阳性表达率为64.1%(50/78),MFI为范围为29.6~193.7,而MCL患者中CD160均为阴性.CD160在典型及不典型CLL中的阳性率均明显高于MCL,差异有统计学意义(χ2分别为51.16,51.81,P<0.01);在CD5-的SBL中CD160+阳性率为1.1%(1/87),CD160在典型及非典型CLL中的阳性率均明显高于CD5-的SBL,差异有统计学意义(χ2分别为80.00,80.02,P<0.01).51例CD160-的CLL中IGH重排率为31.6%(18/51),87例CD160+CLL患者的IGH重排率为62.1%(54/87),CD160+CLL患者的IGH重排率高于CD160-CLL患者,差异有统计学意义(χ2=9.24,P<0.05).结论CD160+对于辅助诊断CLL有重要价值,尤其有助于不典型CLL和MCL以及其他类型SBL的诊断和鉴别诊断.

Objective To analyze the expression of CD160 antigen in patients with chronic lymphocytic leukemia (CLL), and to explore its clinical diagnostic value as well as the correlation of CD160 with genetic abnormalities. Methods A retrospective study was conducted from January 2015 to December 2017. Clinical data of 336 patients in the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province) were collected. Among them, 200 patients were diagnosed with CLL according to WHO Classification Tumors of Hematopoietic and Lymphoid Tissues (the 4th edition of 2008), including 122 patients with typical CLL and 78 with atypical CLL based on Royal Marsden Hospital Immunomarker Integral System. Besides, there were 49 patients diagnosed with MCL and 87 patients with CD5-small B cell lymphoma (SBL). All patients′ tumor cells were detected for CD160 expression and its mean fluorescence intensity (MFI) by flow cytometry. At the same time, fluorescence in situ hybridization (FISH) was used to detect P53 deletion, 13q14 deletion, ATM deletion, 6q23 deletion,+12 and IGH rearrangement in CLL cases. Molecular characteristics and genetic abnormalities were compared between CD160+ and CD160-CLL patients. Results The CD160 positive rate in typical CLL patients and atypical CLL patients was 59.8%(73/122) and 64.1%(50/78), with MFI ranging from 14.9 to 173.9, and 29.6 to 193.7, respectively;while the CD160 positive rate in patients with CD5-SBL was 1.1%(1/87) and all the MCL patients were CD160 negative. The CD160 positive rate was significantly higher in typical and atypical CLL patients than that in MCL patients or patients with CD5-SBL (P<0.01). The rearrangement rate of IGH was significantly higher in CD160+ CLL patients than that in CD160-CLL patients (62.1% vs 31.6%, P<0.05). Conclusion CD160 has significant value for auxiliary diagnosis of CLL, especially can provide a reliable evidence for the diagnosis and differential diagnosis among atypical CLL, MCL, and SBL.