Although the majority of patients with follicular lymphoma (FL) harbor the t(14;18)(q32;q21) IGH/BCL2 gene rearrangement that leads to the overexpression of BCL2 protein, approximately 20% of FL cases lack t(14;18)(q32;q21). It is considered that BCL2 overexpression underscores the development of the majority of cases of FL and their transformation to more aggressive lymphoma [known as transformed FL (tFL)]. However, FL cases lacking the t(14;18)(q32;q21) translocation exhibit symptoms analogous to their t(14;18)‑positive counterparts. An important goal of recent research on FL has been to clarify the distinctions between the two different forms of FL. Numerous studies have shed light onto the genetic and molecular features of t(14;18)‑negative FL and the related clinical manifestations. In this review, we summarize the current knowledge of t(14;18)‑negative FL occurring in the lymph nodes with an emphasis on the underlying molecular and clinical features. In addition, novel treatment directions are discussed.
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