Nückel Holger, Switala Magdalena, Collins Crista H, Sellmann Ludger, Grosse-Wilde Hans, Dührsen Ulrich, Rebmann Vera
Department of Haematology, University of Duisburg-Essen, Germany.
Clin Immunol. 2009 Jun;131(3):472-80. doi: 10.1016/j.clim.2009.02.004. Epub 2009 Mar 24.
CD49d plays a critical role in leucocyte trafficking, activation and survival, and facilitates interactions between leucocytes and stromal cells. Recent data give evidence for the prognostic relevance of CD49d protein expression in B-CLL. In our study we analyzed both the expression of CD49d protein and mRNA in a cohort of 101 CLL patients. The percentage of leukemic B-cells expressing CD49d determined by flow cytometry ranged from 0 to 100%. 37 patients with high CD49d protein expression >or=45% (according to ROC analysis) had a significantly shorter treatment-free survival (TFS) and overall survival (OS) than 64 patients with low CD49d expression (median TFS: 116 versus 43 months, p=0.015; median OS: not reached in both groups, p=0.018). CD49d protein expression was strongly associated with CD38 status (p=0.0001) and ZAP-70 status (p=0.03) but not with IGVH mutation. In multivariate analysis high CD49d expression was a significantly independent prognostic factor (HR 3.0; p=0.005). According to the strong correlation of CD49d protein expression with CD49d mRNA expression (r=0.39; p<0.0001) we could confirm the results on mRNA level with worse prognosis for patients with high mRNA level. Collectively, our data confirm the prognostic significance supporting the idea to use CD49d as target molecules for therapeutic approaches in B-CLL.
CD49d在白细胞迁移、激活和存活中起关键作用，并促进白细胞与基质细胞之间的相互作用。最近的数据证明了CD49d蛋白表达在B细胞慢性淋巴细胞白血病（B-CLL）中的预后相关性。在我们的研究中，我们分析了101例CLL患者队列中CD49d蛋白和mRNA的表达情况。通过流式细胞术测定的表达CD49d的白血病B细胞百分比范围为0至100%。37例CD49d蛋白高表达（≥45%，根据ROC分析）的患者与64例CD49d低表达患者相比，无治疗生存期（TFS）和总生存期（OS）显著缩短（中位TFS：116个月对43个月，p = 0.015；中位OS：两组均未达到，p = 0.018）。CD49d蛋白表达与CD38状态（p = 0.0001）和ZAP-70状态（p = 0.03）密切相关，但与免疫球蛋白重链可变区（IGVH）突变无关。在多变量分析中，高CD49d表达是一个显著的独立预后因素（风险比3.0；p = 0.005）。根据CD49d蛋白表达与CD49d mRNA表达的强相关性（r = 0.39；p < 0.0001），我们可以在mRNA水平上证实高mRNA水平患者预后较差的结果。总体而言，我们的数据证实了预后意义，支持将CD49d用作B-CLL治疗方法的靶分子的观点。
