Rel A is an independent biomarker of clinical outcome in chronic lymphocytic leukemia

Hewamana, Saman, Lin, Thet Thet, Rowntree, Clare, Karunanithi, Kamaraj, Pratt, Guy, Hills, Robert Kerrin ORCID: https://orcid.org/0000-0003-0166-0062, Fegan, Christopher Daniel ORCID: https://orcid.org/0000-0001-9685-0621, Brennan, Paul ORCID: https://orcid.org/0000-0001-8792-0499 and Pepper, Christopher John 2009. Rel A is an independent biomarker of clinical outcome in chronic lymphocytic leukemia. Journal of Clinical Oncology 27 (5) , pp. 763-769. 10.1200/JCO.2008.19.1114

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Abstract

Purpose: We recently demonstrated the biologic importance of the nuclear factor kappa B (NF-κB) subunit Rel A in chronic lymphocytic leukemia (CLL) and hypothesized that Rel A DNA binding would have prognostic significance in this disease. Patients and Methods: Rel A DNA binding was quantified in nuclear extracts derived from 131 unselected CLL patient samples using a quantitative DNA-binding enzyme-linked immunosorbent assay–based method. We then investigated the ability of Rel A to predict for the requirement for treatment and survival and compared our findings with other established prognostic markers. Results: Rel A DNA binding was strongly associated with advanced Binet stage (P < .0001) but did not correlate with immunoglobulin VH (IgVH) mutation status (P = .25), CD38 expression (P = .87), or zeta-chain–associated protein kinase 70 (ZAP-70) expression (P = .55). It was predictive of time to first treatment (P = .02) and time to subsequent treatment (P = .0001). In addition, Rel A was the most predictive marker of survival both from date of diagnosis (hazard ratio [HR], 9.1; P = .01) and date of entry into the study (HR, 3.9; P = .05) and retained prognostic significance in multivariate analysis for both time to first treatment and overall survival in the presence of Binet stage, IgVH mutation status, CD38, and ZAP-70. Conclusion: Rel A is an independent prognostic marker of survival in CLL and seems to have the unique capacity to predict the duration of response to therapy. Prospective assessment of Rel A as a marker of clinical outcome and as a therapeutic target are now warranted.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Publisher:	American Society of Clinical Oncology
ISSN:	0732-183X
Funders:	Leukemia Research (UK), Leukemia Research Appeal for Wales, Welsh Bone Marrow Transplant Research Fund.
Last Modified:	06 Nov 2022 14:19
URI:	https://orca.cardiff.ac.uk/id/eprint/29208

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