title: Early steps of follicular lymphoma pathogenesis.
abstract: Follicular lymphoma (FL) pathogenesis is a complex and fascinating multi-hit process, escalating along successive derailments of the distinctive molecular and cellular mechanisms paving B-cell differentiation and activation. This progressive subversion of B-cell receptor diversification mechanisms and B-cell homeostasis likely occurs during a protracted preclinical phase of asymptomatic growth, in which premalignant clones already disseminate and establish "niches" in secondary lymphoid organs. Following FL diagnosis, a parallel indolent behavior is observed in most patients, slowly progressing over a period of many years, to eventually generate a highly refractory (and in some case transform into an aggressive subtype of) lymphoma. Novel insights in human germinal center B-cell biology recently allowed a more comprehensive understanding of the various illegitimate events sequentially involved in the premalignant progression phases. In this review, we will discuss how these new data have modified our perception of early FL pathogenesis, the new questions and challenges it opened up, and how this knowledge could impact on innovative programs of early detection, follow-up, and patient management.
authors.affiliation: Center of Immunology of Marseille-Luminy (CIML), Université de la Méditerranée, Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roulland
authors.forename: Mustapha
authors.initials: M
authors.lastname: Faroudi
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Sungalee
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nadel
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D019254:Genes, bcl-2; D006801:Humans; D008213:Lymphocyte Activation; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D011961:Receptors, Fc / Q000096:biosynthesis; D014178:Translocation, Genetic
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D011961:Receptors, Fc; C035311:immunoglobulin M receptor