EBV Reactivation and Chromosomal Polysomies: Euphorbia tirucalli as a Possible Cofactor in Endemic Burkitt Lymphoma

Burkitt lymphoma is endemic in the Equatorial Belt of Africa, its molecular hallmark is an activated, MYC gene mostly due to a chromosomal translocation. Especially in its endemic clinical variant, Burkitt lymphoma is associated with the oncogenic Epstein-Barr virus (EBV), and holoendemic malaria acts as an amplifier. Environmental factors may also cooperate in Burkitt lymphomagenesis in the endemic regions, such as plants used as traditional herbal remedies. Euphorbia tirucalli, a plant known to possess EBV-activating substances, has a similar geographical distribution to endemic Burkitt's Lymphoma and is used as a hedge, herbal remedy and toy in the Lymphoma BeltI. In this study we aimed at determining if exposure to Euphorbia tirucalli could contribute to lymphomagenesis, and at which extent. Lymphoblastoid and cord blood-derived cell lines were treated with plant extracts, and the expression of EBV-coded proteins was checked, to assess EBV reactivation. The occurrence of chromosomal translocations was then investigated by FISH. Our preliminary results suggest that E. tirucalli is able to reactivate EBV and determine chromosomal alterations, which leads to c-MYC altered expression. The existence of genomic alterations might determine the accumulation of further genetic alteration, which could eventually lead to a transformed phenotype

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples

A particular extra-nodal lymphoma type arises from B cells of the marginal zone (MZ) of mucosa-associated lymphoid tissue (MALT). The aetiology ofMZ lymphomas suggests that they are associated with chronic antigenic stimulation by microbial pathogens, among which Helicobacter pylori-associated gastricMALT lymphoma is the best studied. Recently, MALT lymphomas have been described in the context of chronic conjunctivitis, which can be associated with Chlamydia spp. infection. Studies from Italy showed the presence of Chlamydia psittaci in 87% of ocular adnexal lymphomas (OAL), and C. psittaci has been described in a large part of samples from Austria and Korea as well. However, this finding was not always confirmed by other studies, suggesting that the association with C. psittaci may depend on geographic heterogeneity. Interestingly, none of the studies up to now has been carried out in the African population, where a strong association between infectious agents and the occurrence of human neoplasms has been reported. This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/ INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittacinegative cases, whereas no hypermethylation of this gene was found in C. psittaci-positive cases, suggesting that mechanisms other than promoter hypermethylation lead to p16/ INK4a silencing in C. psittaci-positive cases. We may conclude that the role of epidemiologic, environmental and genetic factors, must be considered in the aetiology of this disease