Abstract 2738: Expression of p73 isoforms regulates proliferation and chemotherapeutic response in diffuse large B-cell lymphoma

Abstract

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). TP73 gene is a member of the p53 tumor suppressor gene family, which is critical in the regulation of cell cycle and apoptosis. TP73 is located in distal 1p36 chromosomal region that is commonly disrupted in DLBCL. TP73 gene function is controlled by a balance between two isoforms with opposing functions, the full length TAp73 protein (pro-apoptotic) and the NH2-terminally truncated ΔNp73 protein (anti-apoptotic by antagonizing both TAp73 and p53). Up-regulated expression of -Np73 isoforms has been reported in activated and germinal center B- cells as compared to very low levels in memory B- cells and follicular mantle cells, suggesting temporal expression of -Np73 isoforms during specific B- cell developmental stages. In the present study we have investigated the biological relevance of p73 isoforms in DLBCL. The DLBCL cell line DHL-16 was transfected with TAp73 encoded mammalian expression vector. The ‘control cells’ comprised of DHL-16 cells transfected with control vector. To evaluate growth differences under basal conditions as well as with serum deprivation, phenotypic comparison was performed between the two cell lines. Further, to evaluate the response to chemotherapy and to determine the differences in transcriptional targets, the p73 transfected and control cells were studied for the expression of p73 transcriptional targets PUMA, BIM, and GRAMD4. TAp73-transfected cells were more sensitive to serum deprivation and chemotherapy and showed an increased expression of the pro-apoptotic p73 transcriptional targets compared to control cells. We transfected DHL-16 cells with a truncated p73 isoform functionally similar to ΔNp73. These ΔNp73-transfected cells were resistant to serum deprivation and chemotherapy and showed a reduction in the expression of the pro-apoptotic p73 transcriptional targets PUMA, BIM, and GRAMD4 compared to control-vector transfected cells. Together, our data demonstrate that modulation of p73 isoform expression can alter the behavior of DLBCL and highlights p73 as a potential new therapeutic target in DLBCL. Note: This abstract was not presented at the meeting. Citation Format: Hesham M. Hassan, Michelle L. Varney, rakesh K. Singh, Bhavana J. Dave. Expression of p73 isoforms regulates proliferation and chemotherapeutic response in diffuse large B-cell lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2738. doi:10.1158/1538-7445.AM2014-2738