Overview of common mechanisms for the pathogenesis of diffuse large B cell lymphoma

The molecular pathogenesis of diffuse large B cell lymphoma (DLBCL) is a complex, multistep process leading to the replication of a malignant clone of germinal or post-germinal B cell origin. While some steps in this pathway have been elucidated, many remain unknown. The majority of DLBCL tumors demonstrate translocations or mutations that result in the increased expression of the B cell lymphoma 6 (BCL-6) gene. Overexpression of BCL-6 leads to downregulation of target genes, including the p53 tumor suppressor gene, which prevents the cells from undergoing apoptosis in response to DNA damage. Up to 20 percent of DLBCL demonstrate mutations or deletions of the p53 tumor suppressor gene. In addition, p53 transcription is at least partially controlled by the BCL-6 gene. Downregulation of p53 expression or expression of mutant p53 products results in a loss of the normal growth-limiting activities of this gene.