Burkitt's lymphoma: new insights into molecular pathogenesis

Abstract

The World Health Organisation classification reports three subcategories of Burkitt's lymphoma (BL)--endemic, non-endemic, and immunodeficiency associated--proposed to reflect the major clinical and genetic subtypes of this disease. These different types of BL have been reviewed and studied by immunohistochemistry and molecular methods. The results point out the heterogeneity of BL and suggest that AIDS related BL may have a different pathogenesis from that of classic BL.

Figure 1

Typical morphological pattern of Burkitt’s lymphoma (Giemsa stained; original magnification, ×375).

Figure 2

In quiescent G0 cells, the nuclear E2F–pRb2/p130 complex is responsible for the active repression of several cellular promoters. After its release into the cell cycle, pRb2/p130 is phosphorylated by G1 cyclin dependent kinases (cdks) and subsequently degraded through a proteosome dependent mechanism, resulting in the derepression of a variety of genes, including p107. The accumulated p107 protein is then able to interact with E2F4 and E2F5, which have been released from pRb2/p130, and associate with cyclin A (cyc A)/cdk2.

Figure 3

(A) In the tumours where the Rb2/p130 gene is mutated, the interaction between individual proteins and E2F family members and the timing of formation of particular protein–E2F complexes during the cell cycle can be deregulated. (B) pRb2/p130 shares, with all members of the retinoblastoma gene family, the ability to interact physically with certain DNA virus oncoproteins, including simian virus 40 large T antigen and adenovirus E1A protein; by this mechanism, pRb2/p130 is inactivated. CDK, cyclin dependent kinase; Cyc A, cyclin A.