An updated understanding of follicular lymphoma transformation.

Although most patients with follicular lymphoma (FL) follow an indolent disease course, some patients experience a critical inflection point when FL transforms into an aggressive lymphoma. Historically, FL transformation is marked by poor outcomes, particularly for patients with previous FL-directed treatment. Compared with FL, transformed FL (tFL) is marked by numerous additional genetic changes, upregulates novel signaling pathways, and arises from an ancestral FL clone with shared FL-initiating mutations. Prediction of tFL risk remains a high-priority area of disease research, with recent work highlighting memory-like B-cell phenotypes associated with transformation risk and implicating critical tumor-immune interactions at transformation emergence. Mechanistic studies provide insight into the role of genetic drivers in determining malignant B-cell phenotypes or reducing microenvironmental dependencies. In parallel, a shifting therapeutic landscape marked by novel immune-based therapeutics is improving outcomes for patients, yet further clinical outcome data in tFL are greatly needed. This review summarizes recent scientific and clinical studies in tFL and provides an updated understanding of the biological basis, diagnosis, and clinical management of tFL. We conclude with a proposed plan of future research aimed at the goal of increasing tFL biologic knowledge and improving outcomes for patients with tFL.