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Agricultural pesticide exposure and the molecular connection to lymphomagenesis.

Abstract

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.

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  • Authors+Show Affiliations

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    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.

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    Source

    The Journal of experimental medicine 206:7 2009 Jul 06 pg 1473-83

    MeSH

    Adult
    Agricultural Workers' Diseases
    B-Lymphocyte Subsets
    Base Sequence
    Chromosomes, Human, Pair 14
    Chromosomes, Human, Pair 18
    Genetic Predisposition to Disease
    Genotype
    Humans
    Lymphoma, Follicular
    Male
    Middle Aged
    Molecular Sequence Data
    Occupational Exposure
    Pesticides
    Phenotype
    Proto-Oncogene Proteins c-bcl-2
    Translocation, Genetic

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19506050

    Citation

    Agopian, Julie, et al. "Agricultural Pesticide Exposure and the Molecular Connection to Lymphomagenesis." The Journal of Experimental Medicine, vol. 206, no. 7, 2009, pp. 1473-83.
    Agopian J, Navarro JM, Gac AC, et al. Agricultural pesticide exposure and the molecular connection to lymphomagenesis. J Exp Med. 2009;206(7):1473-83.
    Agopian, J., Navarro, J. M., Gac, A. C., Lecluse, Y., Briand, M., Grenot, P., ... Roulland, S. (2009). Agricultural pesticide exposure and the molecular connection to lymphomagenesis. The Journal of Experimental Medicine, 206(7), pp. 1473-83. doi:10.1084/jem.20082842.
    Agopian J, et al. Agricultural Pesticide Exposure and the Molecular Connection to Lymphomagenesis. J Exp Med. 2009 Jul 6;206(7):1473-83. PubMed PMID: 19506050.
    * Article titles in AMA citation format should be in sentence-case
    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 - http://jem.rupress.org/cgi/pmidlookup?view=long&pmid=19506050 DB - PRIME DP - Unbound Medicine ER -