Prognostic impact of Epstein-Barr Virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia
Prognostic impact of Epstein-Barr Virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia
复制标题
慢性淋巴细胞白血病诊断时 Epstein-Barr 病毒 (EBV)-DNA 拷贝数的预后影响。
DOI：
10.18632/oncotarget.6281
复制
发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Liang, Jin-Hua;Gao, Rui;Xu, Wei
在一些慢性淋巴细胞白血病 (CLL) 患者诊断时，他们的血液中检测到了 Epstein-Barr 病毒 (EBV)-DNA。这对于 CLL 的发生或进展是否重要尚存在争议。我们对 243 名新诊断的连续 CLL 受试者的血液 EBV-DNA 拷贝数与生物学和临床变量之间的关联进行了调查。通过实时定量 PCR (RQ-PCR) 进行 EBV-DNA 拷贝的定量。所有受试者都有既往 EBV 感染的血清学证据。然而，只有 24 名受试者 (10%) 在诊断时 EBV-DNA 检测呈阳性。与 EBV-DNA 阴性受试者相比，诊断时 EBV-DNA 阳性受试者的血红蛋白浓度和血小板水平较低，胸苷激酶 1 和血清铁蛋白水平较高，IGHV 基因未突变，且发生里氏转化的风险较高。诊断时 EBV-DNA 阳性受试者的 CD20、CD148 和 ZAP70 阳性细胞百分比以及每个簇名称的平均荧光强度 (MFI) 也有所增加。 EBV-DNA 检测阳性与较短的治疗时间间隔（HR 1.85；[95% 置信区间，1.13，3.03]；P=0.014）和较差的生存率（HR 2.77；[1.18，6.49]；P=0.019）相关。 EBV 拷贝数的减少与治疗反应显着相关。诊断时的血液 EBV-DNA 检测呈阳性以及治疗期间 EBV 拷贝的连续检测与生物学和临床变量、治疗时间、治疗反应和生存显着相关。如果经过验证，这些数据可能会添加到 CLL 预后评分系统中。
Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems.