Hewamana Saman, Lin Thet Thet, Rowntree Clare, Karunanithi Kamaraj, Pratt Guy, Hills Robert, Fegan Chris, Brennan Paul, Pepper Chris
Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.
J Clin Oncol. 2009 Feb 10;27(5):763-9. doi: 10.1200/JCO.2008.19.1114. Epub 2009 Jan 5.
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.
我们最近证明了核因子κB（NF-κB）亚基Rel A在慢性淋巴细胞白血病（CLL）中的生物学重要性，并假设Rel A与DNA的结合在该疾病中具有预后意义。
采用基于定量DNA结合酶联免疫吸附测定的方法，对131例未经选择的CLL患者样本的核提取物中的Rel A与DNA的结合进行定量分析。然后，我们研究了Rel A预测治疗需求和生存情况的能力，并将我们的研究结果与其他已确立的预后标志物进行比较。
Rel A与DNA的结合与晚期Binet分期密切相关（P <.0001），但与免疫球蛋白V(H)（IgV(H)）突变状态（P =.25）、CD38表达（P =.87）或ζ链相关蛋白激酶70（ZAP-70）表达（P =.55）无关。它可预测首次治疗时间（P =.02）和后续治疗时间（P =.0001）。此外，Rel A是从诊断日期（风险比[HR]，9.1；P =.01）和进入研究日期（HR，3.9；P =.05）起生存的最具预测性的标志物，并且在存在Binet分期、IgV(H)突变状态、CD38和ZAP-70的情况下，对于首次治疗时间和总生存的多变量分析中保留了预后意义。
Rel A是CLL生存的独立预后标志物，似乎具有预测治疗反应持续时间的独特能力。现在有必要对Rel A作为临床结果标志物和治疗靶点进行前瞻性评估。
