Cell of origin of transformed follicular lymphoma

Abstract

Follicular lymphoma (FL) is an indolent disease but transformsin2%to3%of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporalchangesof routinely availablebiomarkers,outcome after transformation, as well as molecular subtypesofTFL.We report that the expressionof IRF4 is anindependent predictor of early transformation (Hazard ratio, 13.3; P