Overview of common mechanisms for the pathogenesis of follicular lymphoma

The molecular pathogenesis of follicular lymphoma (FL) is a complex, multistep process leading to the replication of a malignancy clone of germinal B cell origin. While some steps in this pathway have been elucidated, many remain unknown. The majority of FL tumors demonstrate translocations or mutations that result in the increased expression of the B cell lymphoma 2 (BCL-2) gene. Approximately 85 percent demonstrate a translocation between the long arm of chromosome 18 and the immunoglobulin heavy chain gene on chromosome 14, resulting in the t(14;18)(q32;q21). BCL-2 is an anti-apoptotic factor that prevents caspase activation, thereby resulting in prolonged cell survival. Overexpression of BCL-2 is not sufficient to cause FL, and additional factors, such as the tumor microenvironment and other genetic lesions, likely contribute to the pathogenesis.