Grywalska Ewelina, Roliński Jacek, Pasiarski Marcin, Korona-Glowniak Izabela, Maj Maciej, Surdacka Agata, Grafka Agnieszka, Stelmach-Gołdyś Agnieszka, Zgurski Michał, Góźdź Stanisław, Malm Anna, Grabarczyk Piotr, Starosławska Elżbieta
Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland; St. John's Cancer Center, Lublin, Poland.
Department of Hematology, Holycross Cancer Center, Kielce, Poland.
PLoS One. 2015 Oct 13;10(10):e0140178. doi: 10.1371/journal.pone.0140178. eCollection 2015.
Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.
爱泼斯坦-巴尔病毒（EBV）是一种普遍存在的γ疱疹病毒，全球超过90%的人口受其感染。EBV在慢性淋巴细胞白血病（CLL）临床病程中的潜在作用仍不清楚。本研究的目的是确定CLL患者外周血单个核细胞（PBMC）中的EBV-DNA载量是否会影响疾病进程中的异质性。该研究纳入了115例未经治疗的CLL患者（54例女性和61例男性）以及40例健康对照者（16例女性和24例男性）的外周血样本。我们分析了PBMC中EBV-DNA载量与疾病分期、不良预后因素及临床结局之间的关联。115例CLL患者中有62例（53.91%）在PBMC中检测到可检测数量的EBV-DNA拷贝。在需要早期进行治疗、淋巴细胞计数倍增时间<12个月、表现为CD38阳性或ZAP-70阳性表型以及存在del(11q22.3)细胞遗传学异常的患者中，EBV-DNA拷贝数/μg DNA显著更高。此外，EBV-DNA拷贝数/μg DNA与乳酸脱氢酶（LDH）和β2微球蛋白的浓度呈显著正相关。我们已经表明，在CLL患者中，较高的EBV-DNA拷贝数预示着生存期较短和疾病进展时间较短，并且它与其他已确定的不良预后因素相关。这表明EBV可能对CLL的预后产生负面影响。
