Figure 1.

A cartoon showing a simple pathogenesis model of Burkitt lymphoma (BL) showing progression from a naïve B cell through a necessary pre-malignant stage involving chromosomal translocation of MYC on chromosome 8 into the vicinity of promoter elements of immunoglobulin genes on chromosome 14, 2, or 22 and progression of translocation-positive B cells to a clone of malignant BL. The first stage is indicated by letter a and the second stage by letter b. The transit times for these stages are unknown, but several assumptions are possible. First, exogenous exposures linked to high risk of BL, such as infection with malaria, Epstein-Barr virus, and human immunodeficiency virus (HIV) – in the West – may act by increasing the absolute number (load) of translocation-positive B cells, which would increase the number of initiated cells that can progress to BL and, hence, population incidence of BL. Second, the rate-limiting step of BL is the apoptosis feedback loop in translocation-positive B cells. Thus, exposures that increase the survival, i.e., circumvent apoptosis feedback loops in translocation-positive B cells until the abnormal cells develop capacity for self-perpetuation will increase the individual risk of BL.