TY - JOUR T1 - Agricultural pesticide exposure and the molecular connection to lymphomagenesis. AU - Agopian,Julie, AU - Navarro,Jean-Marc, AU - Gac,Anne-Claire, AU - Lecluse,Yannick, AU - Briand,Mélanie, AU - Grenot,Pierre, AU - Gauduchon,Pascal, AU - Ruminy,Philippe, AU - Lebailly,Pierre, AU - Nadel,Bertrand, AU - Roulland,Sandrine, Y1 - 2009/06/08/ PY - 2009/6/10/entrez PY - 2009/6/10/pubmed PY - 2009/7/30/medline SP - 1473 EP - 83 JF - The Journal of experimental medicine JO - J Exp Med VL - 206 IS - 7 N2 - 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. SN - 1540-9538 UR - https://www.unboundmedicine.com/medline/citation/19506050/full_citation L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.20082842 DB - PRIME DP - Unbound Medicine ER -