The expression of p53 was demonstrated in non-T non-B cells and Burkitt's lymphoma cell lines, but neither in two myeloid leukemia cell lines nor in normal lymphoid cells after mitogenic stimulation. p53 expression was demonstrated in 7 cases (2 AML, 5 ALL) but only in ALL cases the percentage of positive of cells was over 20%.
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.
These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.
Cells from acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma cell lines express elevated levels of p53, while all examined human acute myeloid leukemia cell lines synthesize negligible p53 protein.
Further analysis of the BL lines in which p53 had been characterized showed that whereas some lines were essentially resistant to cisplatin, three were rapidly induced to undergo apoptosis.
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.
We investigated temporal relationships between ionizing radiation-induced G1 arrest and induction of the p53-regulated genes GADD45, CIP1/WAF1, and MDM2 in a series of Burkitt's lymphoma and lymphoblastoid cell lines that differed in p53 gene status.
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.
The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively.
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.
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.
We have shown here that in 70% of Burkitt lymphoma cell lines, but not in normal EBV transformed B cell lines, p53 protein is readily detectable by Western blot analysis using either an antibody directed against the 240 epitope or an antibody against wild-type p53.
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).
The viral-associated diseases, Adult T-cell Leukemia (ATL) and Burkitt's lymphoma, showed higher p53 mutation frequencies of 24% and 41%, respectively.
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.
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.