Evolution of classic Hodgkin lymphoma in correlation to changes in the lymphoid organ structure of vertebrates.

In order to integrate evolutionary concepts into lymphoma research we mapped features of classic Hodgkin lymphoma (a disease which has been recently described to be derived from germinal center B-cells) onto a phylogenetic tree of vertebrates. Secondly, we matched the phylogenetic occurrence of classic Hodgkin lymphoma to the changes in the lymphoid organ structure during vertebrate evolution. According to our analysis, classic Hodgkin lymphoma evolved exclusively at the developmental stage of mammals. Interestingly the appearance of Hodgkin lymphoma is correlated to the evolution of germinal centers in mammals. This lends some credit to the hypothesis that genes specific to the germinal center reaction are involved in the pathogenesis of Hodgkin lymphoma. However, as evolution did not stop at the developmental stage of the mammalian stem-species, to a certain extent species with specific differences of classic Hodgkin lymphoma can be expected. One such difference is that classic Hodgkin lymphoma occurs with a significantly higher frequency in humans than in all other mammals. This could be partially due to Epstein-Barr virus (EBV) infection in approximately 40%-50% of Hodgkin disease cases, that is associated with an expression of the EBV-encoded oncogen LMP-1. In conclusion we propose that the mapping of lymphoma related characteristics onto a phylogenetic tree is a valuable new tool in lymphoma research.