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)-positive cells in healthy individuals as clonal lymphoma precursors or indicators of risk is still unclear. We determined the age dependent prevalence and frequency of BCL2/IgH rearrangements in 715 healthy individuals ranging from newborns to octo- and nonagenarians. 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/IgH 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 (18–26 × 10−6) was significantly higher than in younger subjects (7–9 × 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;18)-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;18)-positive cells in healthy individuals as a risk marker toward the development into lymphoma precursors.

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Circulating t(14;18)-positive cells were detected by quantitative real-time polymerase chain reaction on DNA isolated from peripheral blood mononuclear cells (PBMNCs) from 644 healthy individuals between <1 and 91 years of age. In all, 45% of all samples (287/644) were positive, and 40% of the positive samples (114/287) contained more than one positive clone. The prevalence of t(14;18)-positive cells showed a strong correlation with age. A total of 36 cord blood samples and 48 PBMNCs from children <10 years were negative. The prevalence of circulating positive cells increased from the second to fifth decade of life from 20% to 66% and remained stable thereafter. Also the median frequency of circulating t(14;18)-positive cells as well as the prevalence of multiple clones showed an increase with age. In all, 4% (24/644) of all blood samples contained >1 positive cell in 25,000 cells, a finding restricted to healthy individuals >40 years. These results are discussed in relation to the low incidence of follicular lymphoma.

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