Molecular Pathogenesis of Follicular Lymphoma and Its Relevance to Clinical Practice

Abstract

Introduction Our understanding of the molecular basis of follicular lymphoma (FL) has come a long way since the identification of the reciprocal chromosomal translocation, t(14;18), heralded as the primary genetic hallmark.1 Over thirty years on, we are approaching a near-complete catalogue of the genetic underpinnings of this lymphoma subtype, primarily ushered in by technological advancements, such as next-generation sequencing. What is apparent from recent studies is that most FL tumours harbour t(14;18) together with additional genetic alterations, affecting numerous biological pathways, particularly genes involved in epigenetic regulation.2 Moreover, the relapsing-remitting pattern of FL has provided the opportunity to trace the life history and patterns of genetic heterogeneity within an individual patient as their disease evolves and progresses in space and time. There is a recognised diversity in clinical behaviour. Subsets of patients with high-risk phenotypes, including early progressors and those who experience transformation to a high-grade lymphoma, remain priority areas of unmet need given the inferior outcomes,3,4 although the molecular drivers behind such clinical behaviours remain incompletely understood.