In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4412-4412
Abstract:
NF-kB is frequently over expressed in variety of NHL and has been implicated in lymphomagenesis; however, its role in diffuse large B-cell lymphoma (DLBCL) as a prognostic biomarker has not been fully elucidated. Therefore, we investigated the role of NF-kB and its association with clinico-pathological features in a tissue microarray cohort of 230 DLBCL patient samples. We then elucidated the role of NF-kB inhibition on cell viability and apoptosis in-vitro using DLBCL cell lines. Using immunohistochemistry, NF-kB was detected in 25.6% (52/203) DLBCL tumors, was associated with activated B cell (ABC) phenotype (p=0.0054) and overexpression of anti apoptotic marker, XIAP (p=0.0013). DLBCL with nuclear expression of NF-kB showed a significantly poor overall survival as compared to those with no NF-kB expression (p=0.0236). In the multivariate analysis using Cox Proportional Hazard model for IPI and NF-kB expression, the relative risk was 2.97 for high NF-kB expression (95% CI 1.27-6.94; p=0.0113) and 7.55 for high IPI group (95% CI 3.34-18.35; p & lt;0.0001). In-vitro, Bay11-7085 inhibited constitutively active NF-kB expression in a dose dependent manner. Inhibition of NF-kB also down-regulated expression of down-stream target gene products, such as Bcl-2, Bcl-Xl, XIAP and Survivin leading to apoptosis via the mitochondrial apoptotic pathway. NF-kB overexpression was found to be an independent prognostic marker for poor survival in DLBCL. Inhibition of NF-kB caused apoptosis via activation of the mitochondrial apoptotic pathway. Altogether, these results suggest that NF-kB may be a useful prognostic biomarker and a potential target for therapeutic intervention in DLBCL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4412. doi:10.1158/1538-7445.AM2011-4412
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-4412
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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