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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, Fegan, Christopher Daniel, Brennan, Paul 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: 09 Apr 2018 19:40
URI: http://orca-mwe.cf.ac.uk/id/eprint/29208

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