Prevalence and frequency of circulating (14;18)-MBE translocation carrying cells in healthy individuals

Abstract

The t(14;18) translocation is a common genetic aberration that can be seen as an early step in pathogenesis of follicular lymphoma (FL). The significance of low level circulating t(14;18)-posi tive cells in healthy individuals as clonal lymphoma precursors or indicators of risk is still unclear. We determined the age depend ent prevalence and frequency of BCL2/IgH rearrangements in 715 healthy individuals ranging from newborns to octo- and nona genarians. These results were compared with number of circulating t(14;18)-positive cells in 108 FL patients at initial presentation. The overall prevalence of BCL2/lgH junctions in this large sample was 46% (327/715). However, there was a striking dependence upon age. Specifically, among individuals up to 10 years old, none had detectable circulating t(14;18)-positive cells. In the age groups representing 10-50 years old, we found a steady elevation in the prevalence of BCL2/IgH junctions up to a prevalence of 66%. Further increases of the prevalence in individuals older than 50 years were not seen. The mean frequency of BCL2/IgH junctions in healthy individuals ≥40 years 118-26 x 10 -6) was significantly higher than in younger subjects (7-9 X 10 -6). Four percent (31/ 715) of individuals carried more than one t(14;18)-positive cell per 25,000 peripheral blood mononuclear cells (PBMNCs), In comparison, 108 stage III IV FL patients had a median number of circulating t(14;lS)-positive malignant FL cells of about 9200/1 million PBMNCs (range 7-1,000,000). These findings will further improve the understanding of the relevance of t (14;lS)-positive cells in healthy individuals as a risk marker toward the development into lymphoma precursors. © 2008 Wiley-Liss, Inc.