Skip to main content

RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma.

Publication ,  Journal Article
Zhang, M; Xu-Monette, ZY; Li, L; Manyam, GC; Visco, C; Tzankov, A; Wang, J; Montes-Moreno, S; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G ...
Published in: Aging
December 2016

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-kB subunits and involved in the classical NF-kB 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-kB 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 expression profiling 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 B-cell-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 early-stage DLBCL patients, and therapeutic targeting RelA/p65 is effective in inhibiting proliferation and survival of DLBCL with NF-κB hyperactivation.

Duke Scholars

Published In

Aging

DOI

EISSN

1945-4589

ISSN

1945-4589

Publication Date

December 2016

Volume

8

Issue

12

Start / End Page

3321 / 3340

Related Subject Headings

  • Transcription Factor RelA
  • Signal Transduction
  • NF-kappa B
  • Middle Aged
  • Male
  • Lymphoma, Large B-Cell, Diffuse
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, M., Xu-Monette, Z. Y., Li, L., Manyam, G. C., Visco, C., Tzankov, A., … Young, K. H. (2016). RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma. Aging, 8(12), 3321–3340. https://doi.org/10.18632/aging.101121

Published In

Aging

DOI

EISSN

1945-4589

ISSN

1945-4589

Publication Date

December 2016

Volume

8

Issue

12

Start / End Page

3321 / 3340

Related Subject Headings

  • Transcription Factor RelA
  • Signal Transduction
  • NF-kappa B
  • Middle Aged
  • Male
  • Lymphoma, Large B-Cell, Diffuse
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female