Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma in the Western world. It is an indolent disease in most patients, but about 20% of patients experience an early relapse after initial treatment, which is associated with shorter overall survival. A histological transformation into an aggressive lymphoma, most frequently diffuse large-cell B-lymphoma, represents another prognostically unfavorable event in the course of the disease. Thanks to recent genomic studies and mouse models, we are able to better understand the molecular nature of the FL onset and evolution of "aggressive" subclones of cells. Recently, deregulation of several molecular pathways associated with the histological transformation has also been described.
Purpose: This review summarizes the complex molecular mechanisms responsible for FL onset, progression, aggressiveness, and transformation. We believe that the observations in FL have some general implications for understanding the mechanisms leading to the evolution of cancer "aggressiveness," such as divergent evolution, intraclonal variability and tumor plasticity.
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