These observations suggest that the p53 gene alteration may play an important role in lymphomagenesis and/or disease progression in some types of B-cell lymphoma.
We identified 122 patients diagnosed as having large B-cell lymphoma (44, MYC-negative; 29, MYC-EC; 23, MYC rearrangement; 22, MYC and BCL2 rearrangements; 4, MYC, BCL2, and BCL6 rearrangements). p53 expression significantly correlated with DLBCL with abnormal MYC status (MYC-EC, MYC rearrangement, and MYC overexpression), but adverse p53 prognostic effect was only seen with MYC-rearranged lymphoma.
The DEGs were as follows: Phosphatidylinositol‑dependent kinase 1 (PDK1), a key gene upstream of protein kinase B (AKT); angiopoietin 2, a B‑cell lymphoma 2 (Bcl‑2)‑inhibited gene; transcription factor 4, glutathione S‑transferase P91 and ubiquitin‑specific protease 33, mitogen‑activated protein kinase (MAPK)‑related genes; oxidative stress induced growth inhibitor 1, related to the P53 pathway; Bcl‑2, P53, ERK (MAPK1/3), c‑Jun N‑terminal kinase (MAPK8/9), and P38 (MAPK14), all of which are key genes involved in the AKT signaling pathway.
The high frequency of p53 mutation in NHL B cell lines and the relatively low frequency of p53 mutations in fresh lymphoma tissue suggests that p53 gene alteration may play a role in lymphomagenesis and/or disease progression in a subset of B cell lymphomas and that the p53 mutation conveys a proliferative advantage on lymphoma cells that permits their in vitro growth.
Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma.
Among the most frequent alterations conferring resistance, we observed somatic and insertional loss-of-function mutations in transformation-related protein 53 (<i>Trp53</i>) in 54% of tumors and transposon-mediated gain-of-function alterations in B-cell lymphoma-extra large (<i>Bcl-xL</i>), <i>Mdm4</i>, and two <i>TP53</i> family members, resulting in expression of the TP53 dominant negative truncations <i>ΔNTrp63</i> and <i>ΔNTrp73.</i> Enhanced BCL-xL and MDM4 protein expression was confirmed in resistant tumors, as well as in HDM201-resistant patient-derived tumor xenografts.
In contrast, STAT5(S711F) was found to cooperate with the loss of function of the p53 tumor suppressor gene to both accelerate disease onset and to skew the large tumor spectrum that normally characterize p53-deficient mice to strongly favor B-cell lymphoma/leukemia.
These data indicate that with the exception of Burkitt lymphomas, p53 mutations are not involved in the majority EBV-positive B-cell lymphomas which develop in immunocompromised patients.
Mice with HSC deletion of Tp53 predominantly succumbed to thymic lymphomas with clonal translocations not involving Tcr loci; however, these mice occasionally developed mature B-cell lymphomas that harbored clonal Ig translocations.
To assess a possible role of EBV infection, p53 protein deregulation, and p53 gene alterations in exons 5 to 8, we have studied six cases of HIV-related primary oral large B-cell lymphoma.
MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians.
The following research contents were performed: superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities; tumor protein p53 (p53), B cell lymphoma-2 (Bcl-2), B cell lymphoma extra large (Bcl-x), Bcl-2-associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), fas, and caspase-3 messenger RNA (mRNA) expression; and morphologic observation.