t (11; 14)-positive clones can persist over a long period of time in the peripheral blood of healthy individuals

Y Lecluse, P Lebailly, S Roulland, AC Gac, B Nadel… - Leukemia, 2009 - nature.com
Y Lecluse, P Lebailly, S Roulland, AC Gac, B Nadel, P Gauduchon
Leukemia, 2009nature.com
Several lymphoma-and leukaemia-associated chromosomal translocations are present in
the peripheral blood of healthy individuals (HI). Translocation t (14; 18), the genetic hallmark
of follicular lymphoma (FL) that juxtaposes the BCL2 protooncogene near the
immunoglobulin heavy chain (IGH) locus, can be detected in most HI at highly variable
frequency. 1 Individual characteristics, such as smoking habits, viral infection, and
occupational and/or environmental factors (such as pesticide exposure), suspected to play a …
Several lymphoma-and leukaemia-associated chromosomal translocations are present in the peripheral blood of healthy individuals (HI). Translocation t (14; 18), the genetic hallmark of follicular lymphoma (FL) that juxtaposes the BCL2 protooncogene near the immunoglobulin heavy chain (IGH) locus, can be detected in most HI at highly variable frequency. 1 Individual characteristics, such as smoking habits, viral infection, and occupational and/or environmental factors (such as pesticide exposure), suspected to play a role in lymphoma genesis, have been associated with an increase in t (14; 18) translocation frequency. 2 We recently showed that clonotypic t (14; 18)-positive cells can persist in the peripheral blood over a long period of time. 3 High t (14; 18) rates in HI are mainly because of an expanding population of atypical B cells issued from germinal centre that share genotypic and phenotypic features with FL cells. 4 t (14; 18)-positive cells in HI may thus represent much more advanced precursors of the FL pathway than thought earlier.
As t (14; 18) in FL, translocation t (11; 14)(q13; q32) is considered as the primary event in the pathogenesis of mantle cell lymphoma (MCL), a neoplasia that accounts for 5–10% of all non-Hodgkin’s lymphoma. 5 The juxtaposition of the immunoglobulin heavy chain joining region on chromosome 14 to a chromosomal locus on 11q13 places the CCND1/BCL1 gene under the control of the IGH enhancer, resulting in aberrant overexpression of cyclin D1, a positive regulator of the cell cycle. 5 Both t (11; 14) and t (14; 18) translocations are thought to arise from the same mechanism of illegitimate repair of V (D) J recombination intermediates, with recombinase-mediated breaks in the IGH locus and double-stranded breaks of different origins at the oncogene loci. 6 Considering mechanistic and oncogenic similarities between t (14; 18) and t (11; 14), we sought to evaluate the incidence of t (11; 14) in HI and their persistence over time. To date, the presence of t (11; 14)-positive cells in peripheral blood from HI has only been reported in one individual over the hundred HI studied and at a relatively low frequency (Bsix copies in 1 million normal cells). 7 In this paper, we used a sensitive fluctuation nested PCR analysis to determine the prevalence, frequency and long-term evolution of circulating t (11; 14)-positive cells in the peripheral blood of 71 healthy males who had been examined earlier for the t (14; 18) translocation using a similar approach. 2, 3 Twenty
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