Pathogenesis of follicular lymphoma
Robert Kridel, Laurie H. Sehn, Randy D. Gascoyne
Robert Kridel, Laurie H. Sehn, Randy D. Gascoyne
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Review Series

Pathogenesis of follicular lymphoma

Abstract

The hallmark t(14;18)(q32;q21) in follicular lymphoma (FL) results in constitutive overexpression of the BCL2 protein, allowing B cells to abrogate the default germinal center apoptotic program. Most tumors are characterized by recurrent secondary genetic alterations including genomic gains, losses, and mutations, some providing a growth advantage, including alterations in MLL2, EPHA7, TNFRSF14, and EZH2. The sequence in which these events occur and how they contribute to progression and ultimately to transformation is unclear. Lastly, crosstalk between neoplastic B cells and non-neoplastic immune and stromal cells in the microenvironment plays an important role in sustaining tumor cell growth, cultivating immune privilege, and promoting transformation.

Authors

Robert Kridel, Laurie H. Sehn, Randy D. Gascoyne

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Figure 2

A model of the complex pathways leading to progression and transformation in FL.

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A model of the complex pathways leading to progression and transformatio...
Evolution occurs through emergence of traits that provide a growth advantage under selective pressures such as therapy and tumor control by the microenvironment. The circles denote hits that drive somatic cells to malignancy. The progenitor cell may precede overt FL by many years and in roughly 85% of cases harbors a BCL2/IGH rearrangement in addition to putative secondary hits. The progenitor disseminates early during the course of the disease. Clinical FL develops with the acquisition of further genetic alterations and establishment of immune privilege. Relapse occurs either by direct clonal evolution from de novo FL or by indirect evolution from a common ancestral cell. Transformation is thought to develop along similar pathways, but may be dominated by one of a number of key genetic alterations.