Originally published as JCO Early Release 10.1200/JCO.2008.19.1114 on January 5 2009

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Rel A Is an Independent Biomarker of Clinical Outcome in Chronic Lymphocytic Leukemia

From the Department of Haematology; Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff; and the Department of Haematology, Birmingham Heartlands Hospital, Birmingham, United Kingdom.

Corresponding author: Chris Pepper, PhD, Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom; e-mail: peppercj{at}cf.ac.uk.

Purpose We recently demonstrated the biologic importance of the nuclear factor kappa B (NF-B) 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 V_H (IgV_H) 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, IgV_H 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.

Supported in part by grants from Leukemia Research (UK), the Leukemia Research Appeal for Wales, and the Welsh Bone Marrow Transplant Research Fund.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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