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

2009; Lippincott Williams & Wilkins; Volume: 27; Issue: 5 Linguagem: Inglês

10.1200/jco.2008.19.1114

1527-7755

Saman Hewamana, Thet Thet Lin, Clare Rowntree, Kamaraj Karunanithi, Guy Pratt, Robert K. Hills, Chris Fegan, Paul Brennan, Chris Pepper,

Chronic Myeloid Leukemia Treatments

We recently demonstrated the biologic importance of the nuclear factor kappa B (NF-kappaB) subunit Rel A in chronic lymphocytic leukemia (CLL) and hypothesized that Rel A DNA binding would have prognostic significance in this disease.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.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.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.