Agricultural pesticide exposure and the molecular connection to lymphomagenesis.

Julie Agopian (1) , Jean-Marc Navarro (1) , Anne-Claire Gac (2) , Yannick Lecluse (2) , Mélanie Briand (2) , Pierre Grenot (1) , Pascal Gauduchon (2) , Philippe Ruminy (3) , Pierre Lebailly (2) , Bertrand Nadel (1) , Sandrine Roulland (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 GRECAN - Groupe Régional d'Etudes sur le CANcer
3 GPL - Groupe d'étude des proliférations lymphoïdes

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.

Domaines: Immunologie

Julie Agopian, Jean-Marc Navarro, Anne-Claire Gac, Yannick Lecluse, Mélanie Briand, et al.. Agricultural pesticide exposure and the molecular connection to lymphomagenesis.. Journal of Experimental Medicine, 2009, 206 (7), pp.1473-83. ⟨10.1084/jem.20082842⟩. ⟨hal-00408462⟩