We verified that the oncogenic effect of iASPP on Burkitt lymphoma is TAp63 dependent rather than p53 and confirmed that the interaction between CDK1 and iASPP enhanced the inhibitory effect of iASPP on p53 and TAp63.
Immunohistochemical overexpression of p53 protein was found in 21% of NHL patients, with the highest incidence of p53 immunoreactivity in cases of Burkitt's lymphoma, follicle center lymphoma grade III, and diffuse large B-cell lymphoma.
TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases.
Here we show that chloroquine, a drug that activates the stress-responsive Atm-p53 tumor-suppressor pathway, preferentially enhances the death of Myc oncogene-overexpressing primary mouse B cells and mouse embryonic fibroblasts (MEFs) and impairs Myc-induced lymphomagenesis in a transgenic mouse model of human Burkitt lymphoma.
In this study, immunoglobulin variable (Ig V) region genes, c-myc re-arrangement and sequence and p53 status were analyzed in clones derived from a Burkitt's lymphoma cell line (LAM) in which it was previously demonstrated that Epstein-Barr virus (EBV) infection occurred late during lymphomagenesis.
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.