JC human polyomavirus (JCV) and Epstein-Barr virus (EBV) replicative activities are detected in Hodgkin/Reed Sternberg cells (HRS) and circulating lymphocytes (PBL) of Hodgkin lymphoma (HL) and associated with relapse, especially in younger patients

Abstract

7551 Background: The HRS derive from germinal-center B-cells, potential sites for latency and reactivation of JCV in immunosuppressed individuals. Replication of human polyomaviruses (JC, BK, SV40) and EBV was assessed in Hodgkin (HL) and B cell non-Hodgkin (B-NHL) lymphomas. Methods: FISH, immunohistochemistry for oncogenic proteins, PCR and DNA sequencing to identify polyomaviruses and EBV on involved nodes and in PBL before, during and after treatment (N = 73 HL, 91 B-NHL). Controls were 30 healthy donors, 70 solid tumors and 14 acute leukemia patients. Results: using FISH, JCV and EBV DNA were detected in all lymphoma nodes. High genome copy number of JCV and EBV were present in 60% and 63%, respectively, in HL patients versus 11% and 14% in B-NHL patients (P < 10−6; P < 10−5). Using nest-PCR, JCV DNA sequencing after laser capture microdissection identified the presence and specificity of JCV sequences in HRS. T antigen and LMP1 co-expression, in 34% of HRS, was associated with early HL relapse (P < 10−4), particularly in young patients (P < 10−5). Only in HL patients PBL, genome copy number of JCV increased significantly during treatment (42%). Rogue cells (cultured lymphocytes with multiple complex chromosomal aberrations indicative of genomic instability) appeared in 40% of patients, and correlated with relapse (p < 10−4). The same JCV sequences were found in tumor cells and PBL of HL patients. Co-genomic replication of EBV and JCV was highly correlated in lymph nodes and in PBL in HL. Conclusions: JCV genomic replication was detected for the first time in HRS, and associated to rogue cell emergence in PBL. Co-detections of JCV and EBV genomic replication in HRS and PBL are associated with relapse, especially in young patients. HRS and PBL JCV/EBV infections are linked and worth further studies. No significant financial relationships to disclose.