The role of the TP53 gene's R72P polymorphism in non-Hodgkin lymphoma (NHL) has been analyzed in several studies but it has not been studied in Hodgkin lymphoma (HL).
Importantly, an analogous Fas-dependent mechanism of apoptosis upon Nutlin-3 treatment is executed in wild-type p53 expressing Hodgkin lymphoma and acute myeloid leukaemia cell lines.
In this study, we demonstrate that pharmacologic activation of the p53 pathway with the murine double minute 2 (MDM2) antagonist nutlin-3 in Hodgkin lymphoma-derived cell lines leads to effective apoptosis induction and sensitizes the cells to other anticancer drugs.
This study characterizes mutations in TP53 transcripts within cHL cell lines with associated functional defects in the resulting p53 proteins and therefore reintroduces the concept that mutations of TP53 might be involved in the pathogenesis of Hodgkin's lymphoma.
The restriction of the TP53 mutations to the DLBCL in the HL/DLBCL case exemplifies a late transforming event that presumably happened in the germinal center and affected the fate of a common lymphoma precursor cell towards development of a DLBCL.
As the incidence of p53 mutations is significantly lower in Hodgkin's lymphoma than in other neoplasias, we investigated whether the malfunction of other proteins in this pathway could be responsible for its inactivation.