Transfection of the wt p53 gene into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire wt p53 function and rendered it less tumorigenic in mice.
Recent work has shown that p53 gene mutations are frequently found in Epstein-Barr virus (EBV)-positive and EBV-negative cases of Burkitt's lymphoma but not in EBV-associated undifferentiated nasopharyngeal carcinomas (NPCs).
Our results showed that BL cell lines have variable response to DNA-damaging agents that cannot be correlated exclusively with p53 mutation or survivin expression suggesting that p53-independent transactivation may play a role in apoptosis induced by DNA-damaging agents.
We selected a group of 16 patients with acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the presence of p53 mutations.
Our results indicate that the p53 gene is mutated in a majority of Burkitt lymphoma cell lines (BLs), and suggest that p53 mutation contributes to the malignant phenotype of these cell lines.
At least three genetic changes are known to contribute to the genesis of Burkitt's lymphoma (BL): the Ig/myc translocation, the presence of Epstein-Barr virus (EBV) in the vast majority of the endemic and a minority of sporadic tumors, and a p53 mutation, present in approximately 60% of the BL-derived lines.
In hematological malignancies, p53 is most often mutated in Burkitt's lymphoma, with p53 mutations present in 30 to 40% of tumor samples and in 70% of cell lines.
It is hypothesized that this difference with most tumors could be due to the fact that p53 mutations in BL and L3 ALL are generally associated with persistence of a normal residual p53 allele, contrary to what is observed in the majority of tumors.
These results suggest that the lack of CD54 by BL cells may provide the background for the mutation of p53 gene to occur which could result in the transformation to a more aggressive phenotype.
The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected.
The viral-associated diseases, Adult T-cell Leukemia (ATL) and Burkitt's lymphoma, showed higher p53 mutation frequencies of 24% and 41%, respectively.
The present study assessed the role of the p53 tumor suppressor gene in cell cycle arrest and apoptosis following treatment of Burkitt's lymphoma and lymphoblastoid cell lines with gamma-rays, etoposide, nitrogen mustard, and cisplatin.