@article{bcc93e6cc6254e528c8e34beb116d634,
title = "RelA NF-kB subunit activation as a therapeutic target in diffuse large B-cell lymphoma",
abstract = "It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-κB subunits and involved in the classical NF-κB pathway. However, the prognostic and biological significance of RelA/p65 is equivocal in the field. In this study, we assessed RelA/p65 nuclear expression by immunohistochemistry in 487 patients with de novo diffuse large B-cell lymphoma (DLBCL), and studied the effects of molecular and pharmacological inhibition of NF-κB on cell viability. We found RelA/p65 nuclear expression, without associations with other apparent genetic or phenotypic abnormalities, had unfavorable prognostic impact in patients with stage I/II DLBCL. Gene expressionprofiling analysis suggested immune dysregulation and antiapoptosis may be relevant for the poorer prognosis associated with p65 hyperactivation in germinal center B-cell-like (GCB) DLBCL and in activated Bcell- like (ABC) DLBCL, respectively. We knocked down individual NF-κB subunits in representative DLBCL cells in vitro, and found targeting p65 was more effective than targeting other NF-κB subunits in inhibiting cell growth and survival. In summary, RelA/p65 nuclear overexpression correlates with significant poor survival in earlystage DLBCL patients, and therapeutic targeting RelA/p65 is effective in inhibiting proliferation and survival of DLBCL with NF-κB hyperactivation.",
keywords = "Diffuse large B-cell lymphoma, GCB, Gene expression profiling, NF-kB, P65, Proteasome inhibitor, TP53",
author = "Mingzhi Zhang and Xu-Monette, {Zijun Y.} and Ling Li and Manyam, {Ganiraju C.} and Carlo Visco and Alexandar Tzankov and Jing Wang and Santiago Montes-Moreno and Karen Dybkaer and April Chiu and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L.} and Hsi, {Eric D.} and Choi, {William W.L.} and {van Krieken}, {J. Han} and Jooryung Huh and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J.M.} and M{\o}ller, {Michael B.} and Parsons, {Ben M.} and Winter, {Jane N.} and Piris, {Miguel A.} and Medeiros, {L. Jeffrey} and Pham, {Lan V.} and Young, {Ken H.}",
note = "Funding Information: The work was supported by the National Cancer Institute/National Institutes of Health (R01CA138688, R01CA187415, and 1RC1CA146299 to KHY). This work was also partially supported by NSFC (81570203 to MZ and 81570204 to LL), the National Cancer Institute and National Institutes of Health grants P50CA136411 and P50CA142509, and by MD Anderson's Cancer Center Support Grant CA016672. MZ is the recipient of professorship award. KHY is also supported by The University of Texas MD Anderson Cancer Center Institutional Research and Development Fund, an Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award, an MD Anderson Cancer Center Myeloma SPORE Research Development Program Award, a Gundersen Lutheran Medical Foundation Award, the University Cancer Foundation via the Sister institution network Fund at The University of Texas MD Anderson Cancer Cancer and is partially supported by grants from the National Cancer Institute/National Institutes of Health (P50CA136411 and P50CA142509).",
year = "2016",
doi = "10.18632/aging.101121",
language = "English (US)",
volume = "8",
pages = "3321--3340",
journal = "Aging",
issn = "1945-4589",
publisher = "US Administration on Aging",
number = "12",
}