EBV INFECTION AND DISEASE PROGRESSION CELL-SURFACE MARKERS IN LATVIAN COHORT OF UNTREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Objectives. Epstein Barr virus (EBV) is a human virus implicated in oncogenesis of various lymphomas and associated with autoimmune complications. Previously, we demonstrated that EBV infection of B cells induces expression of the chemokine receptors CCR1 and CCR2. Since 2008, WHO classifies chronic
lymphocytic leukemia (CLL), a major type of adult leukemia, as a B-cell NHL. The aim was to assess in untreated CLL patients a relationship between the EBV infection and expression of the cell-surface markers, CCR1, CCR2, and known negative prognostic CD38.
Materials and Methods. The EBV DNA viral load in PB cells was determined using commercial quantitative PCR kit (detection limit: 5 copies/105 cells). mRNA expression of the EBV latent genes, EBNA2, LMP1, and LMP2A, we also examined. We compared the frequency of the CD38-, CCR1-, and CCR2-expressing PB lymphocyte populations, using multiparameter flow cytometry, in 23 EBV-positive and 24 EBV-negative untreated CLL patients. The study was funded by the projects: LZP No.lzp-2018/1-0156We compared the frequency of the CD38-, CCR1-, and R2-expressing PB lymphocyte populations, using multiparameter flow cytometry, in 23 EBV-positive and 24 EBV-negative untreated CLL patients. The study was funded by the projects: LZP No.lzp-2018/1-0156 and RSU No.6-ZD-22/14/2022.
Results. Three patients only had the high viral load exceeding 200 EBV DNA copies/105 PB cells, two of them were with the moderate frequency and one with > 30% of the CD38+ leukemic lymphocytes. The EBV oncogene LMP1 transcription was determined in 3 out of 23 EBV positive patients. Surprisingly, the viral load in these patients was only 6-7 copies/105 cells. The all 3 LMP1-expressing patients were CD38-positive (> 30% of CLL cells). In patients co-expressing LMP1 and EBNA2, CCR1 and CCR2 were also resented on > 30% of the CD19+CD5+ lymphocytes.
Conclusions. Expression of the EBV oncogene LMP1 in PB cells is linked to expression of the negative prognostic marker CD38 and to the increased number of the CCR1- and CCR2-expressing leukemic cells. CCR1/CCR2 on CLL cells can promote dissemination of these cells through the body thus contributing to
progression of the disea se.