Abstract
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.
Highlights
Burkitt’s Lymphoma (BL), a high-grade Non-Hodgkin’s lymphoma, is endemic in the Lymphoma Belt of Africa, which lies between 10◦N and 10◦S of the Equator [1, 2]
Holoendemic malaria acts as an amplifier and has been shown to be able to activate the latent Epstein-Barr virus (EBV) in B-lymphocytes in children in the Equatorial Belt [9, 10]
To assess whether cell death was due to the toxicity effects of the plant extracts or to reactivation of EBV, we treated an EBV-negative cell line using the same experimental conditions, and we observed a similar reduction in cell proliferation accompanied by an increase in cell death suggesting that cell death was due to plant toxicity (Figure 2)
Summary
Burkitt’s Lymphoma (BL), a high-grade Non-Hodgkin’s lymphoma, is endemic in the Lymphoma Belt of Africa, which lies between 10◦N and 10◦S of the Equator [1, 2]. The combination of malaria and early infection with the Epstein-Barr virus is thought to be responsible for boosting the incidence of Burkitt’s lymphoma a hundred-fold in Africa, compared with rates in the France, and the USA [11, 12]. Children who subsequently develop the endemic Burkitt’s Lymphoma have raised antibody levels to the EBV Viral Capsid Antigen (VCA) of EBV several years before they develop the tumour [13]. Raised levels of this antibody are found in the relatives of children
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