Rel a is an independent biomarker of clinical outcome in chronic lymphocytic leukemia.
Hewamana S., Lin TT., Rowntree C., Karunanithi K., Pratt G., Hills R., Fegan C., Brennan P., Pepper C.
PURPOSE: 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. 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.