14 research outputs found
Immunohistochemistry for câmyc and bclâ2 overexpression improves risk stratification in primary central nervous system lymphoma
Distinct chemokine receptor expression profiles in de novo DLBCL, transformed follicular lymphoma, Richterâs trans-formed DLBCL and germinal center B-cells
Immunohistochemistry for câmyc and bclâ2 overexpression improves risk stratification in primary central nervous system lymphoma
Immunohistochemical double hit score enhances NCCN-IPI and is associated with detrimental outcomes in refractory or relapsing patients with diffuse large B cell lymphoma
Immunohistochemical double hit score enhances NCCN-IPI and is associated with detrimental outcomes in refractory or relapsing patients with diffuse large B cell lymphoma
The Role of immunohistochemical overexpression of p53 as adverse prognostic factor in primary testicular diffuse large b cell lymphoma
Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival
Abstract The nuclear orphan receptor NR4A1 functions as tumour suppressor in aggressive lymphomas by pro-apoptotic genomic and non-genomic effects. Here, we immunohistochemically studied the clinico-pathological relevance of NR4A1 protein expression patterns in a cohort of 60 diffuse large B cell lymphoma (DLBCL) patients and non-neoplastic lymph nodes. We observed a significant association between high cytoplasmic NR4A1 and favourable cancer-specific survival and the germinal centre B cell-like subtype, respectively. Moreover, the percentage of lymphoma cells exhibiting cytoplasmic NR4A1 significantly correlated to those showing cleaved caspase 3. Complementary, functional profiling using gene set enrichment of Reactome pathways based on publicly available microarray data was applied to determine pathways potentially implicated in cytoplasmic localization of NR4A1 and validated by means of semi quantitative real-time PCR. The pathway analysis revealed changes in the ERK1/2 pathway, and this was corroborated by the finding that high cytoplasmic NR4A1 was associated with higher expression of ERK1/2 targets in our cohort. These data indicate that high cytoplasmic NR4A1 is associated with a favourable lymphoma-specific survival and highlights the importance of NR4A1 expression patterns as potential prognostic marker for risk assessment in aggressive lymphomas
NR4A3 suppresses lymphomagenesis through induction of proapoptotic genes
Abstract
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas. Cancer Res; 77(9); 2375â86. ©2017 AACR.</jats:p