Prevalence and frequency of circulating t(14;18)‐MBR 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)-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.

Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging

“…In our study population, we detected that this rearrangement was present in 37.8 % of our population, similar to that described in other studies performed in healthy individuals (40-60 %) (Nambiar and Raghavan 2012). Moreover, the frequency of the translocation increased with the age of individuals (30.9 vs 46.2 %), results which were also in line with previous studies Liu et al 1994;Nambiar and Raghavan 2010;Schüler et al 2009). The chromosome translocation BCR-ABL or t(9;22) involving the major region of BCR is found in patients with chronic myeloid leukemia (CML) and adult acute lymphoblastic leukemia (Zhen and Wang 2013).…”

Follicular lymphoma-like B cells of uncertain significance (in situ follicular lymphoma) may infrequently progress, but precedes follicular lymphoma, is associated with other overt lymphomas and mimics follicular lymphoma in flow cytometric studies

“…20 This concept is also consistent with the observation that up to 66% of healthy individuals over the age of ten years have circulating cells with BCL2 translocations, and with the belief that these cells already have many FL-like features and colonize the GC niche. [21][22][23][24][25][26][27] Other non-FL/DLBCL B-cell, T-cell and classical Hodgkin type lymphomas have also been reported in 15-31% of patients with FLBUS. However, whether these bear any relationship to the FLBUS, reflect an increased propensity to develop lymphoma due to genetic or environmental factors, or simply result from the overt neoplasm leading to a tissue biopsy are all unknown.…”

Pediatric follicular lymphoma - a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma - Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials

“…2 A screening of healthy individuals indicated that t(14;18)(q32;q21)-positive B cells are detectable in the peripheral blood starting from the age of 10 years. 22 Thus, positive polymerase chain reaction results suggestive of a t(14;18)(q32;q21) in pediatric patients should be validated by an in situ technique, such as FISH, to prove that the translocation is a feature of the lymphoma cells.…”