The pathogenesis of follicular lymphoma, beyond apoptosis resistance

Follicular lymphoma (FL) is the second most common indolent B-cell lymphoma (1). FL is characterized by a heterogeneous clinical evolution and remains incurable despite recent progress. The accepted founding event of FL pathogenesis is the acquisition of the t(14;18)(q32;q21) during primary VDJ recombination in the bone marrow (2). This chromosomal translocation juxtaposes the antiapoptotic proto-oncogene BCL2 to the immunoglobulin heavy chain locus during VDJ recombination (3). The resulting dysregulation of BCL2 expression provides a survival advantage through activation of antiapoptotic programs. The consequences of this early genetic event become manifest much later during B-cell maturation, when FL cells clonally expand and adopt malignant growth in germinal centers (GC) (2). The precise mechanisms involved in the initiation of malignant growth of apoptosisresistant t(14:18)-positive B-cells remain unclear.