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Agricultural pesticide exposure and the molecular connection to lymphomagenesis.
The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18)(+) non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18)(+) B cells. We further demonstrate that such t(14;18)(+) clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18)(+) clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression.
Centre d'Immunologie de Marseille-Luminy, Institut National de Santé et de Recherche Médicale (INSERM) U631, Centre National de Recherche Scientifique UMR6102, Université de Méditerranée, 13288 Marseilles, France., , , , , , , , ,
Agricultural Workers' Diseases
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 18
Genetic Predisposition to Disease
Molecular Sequence Data
Proto-Oncogene Proteins c-bcl-2
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't