Biology of follicular lymphoma: insights and windows of clinical opportunity.

Follicular lymphoma (FL) is a heterogeneous disease, both clinically and biologically. The biological behavior and development of FL is a culmination of complex multistep processes underpinned by genetic and nongenetic determinants. Epigenetic deregulation through recurrent genetic alterations is now a recognized major biological hallmark of FL, alongside the t(14;18) translocation. In parallel, there is a strong interplay between the lymphoma B cells and the immune microenvironment, with the microenvironment serving as a critical enabler by creating a tumor-supportive niche and modulating the immune response to favor survival of the malignant B cells. A further layer of complexity arises from the biological heterogeneity that occurs between patients and within an individual, both over the course of the disease and at different sites of disease involvement. Altogether, taking the first steps to bridge the understanding of these various biological components and how to evaluate these clinically may aid and inform future strategies, including logical therapeutic interventions, risk stratification, therapy selection, and disease monitoring.