Primary overt follicular lymphoma (FL) emerges from early mutated cancer precursor cells (CPCs) engaged in a dynamic process of re-entry into the germinal centre (GC), evolving and disseminating over decades in asymptomatic individuals. Such early clones are also likely at the origin of post-treatment relapses. FL-like cells (FLLCs) are present in most healthy individuals and will never progress to FL (despite dissemination to different organs and sharing some genotypic and phenotypic features with FL). By contrast, CPCs are more evolved and committed to ultimately give rise to FL. In situ follicular neoplasia (ISFN) represents an early precursor lesion that might progress into FL at a low rate of progression (5%), although its relationship with CPCs remains unknown. In FL, spatial and temporal genomic analysis revealed that relapse events (relapse 2) or transformation to faster-growing high-grade FL (t-FL; relapse 3) arise predominantly by divergent evolution of a common mutated CPC that clonally diverges through the acquisition of distinct genetic events. Relapse events (that is, relapse 1) arising from a direct clonal evolution of the dominant FL clones present at the diagnosis also exist and characterize mostly early progression specimens. HSPC, haematopoietic stem and precursor cell. | Gascoyne, J. et al. Follicular lymphoma: State-of-the-art ICML workshop in Lugano 2015. Hematol. Oncol. 35, 397–407 (2017).
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