DETECTION OF 2 EPSTEIN-BARR-VIRUS (EBV)-CARRYING LEUKEMIC-CELL CLONESIN A PATIENT WITH CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL)

The leukemic-cell population of one CLL patient, PG, was found to cont ain a sub-set of EBV-genome-carrying cells. It was detected directly b y the expression of EBNA (EBV-encoded nuclear antigen) and by its capa city to grow in vitro. The proportion of EBNA-positive cells (0.1%) wa s maintained constantly during the period of this study, the final 3 y ears of the patient's life. EBV-carrying clonal sibling B-cell lines w ere established on 5 occasions. They had identically rearranged JH ban ds and chromosomal markers corresponding to the ex vivo CLL cells. Ana lysis of the viral episomes in the lines proved that they were the des cendants of one cell. On the last occasion of blood sampling, 8 B-cell lines were established; 4 of these contained the same clonal markers as the previous lines, while 4 other lines belonged to another clone w ith identical JH rearrangement. Their abnormal karyotypes were differe nt from the first clone. The chromosomal markers were only partly iden tical, suggesting secondary diversifications. The EBV sub-strain carri ed by this group of lines was different from the sub-strain of the fir st clone, as judged by the EBNA size distributions (EBNOtype) and EBV- DNA analysis. Analysis of the terminal repeat in the viral episomes al so showed that the first and the second set of clones represented 2 in dependent EBV-infection events in vivo. (C) 1995 Wiley-Liss, Inc.