School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
J Pharm Pharm Sci. 2013;16(2):231-7. doi: 10.18433/j3f01c.
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, some patients may survive for many years, while 20-30% of patients progress and may die within several years. Currently, there is not a single procedure that enables accurate prognosis and triaging of those patients who need immediate and aggressive treatment. All CLL cells are characterised by the expression of the B-cell antigens CD19, CD20, CD21, CD22 and CD23, with aberrant expression of the T-cell antigen CD5.
We have developed a CD antibody microarray (DotScan) containing 182 immobilised CD antibodies that has been used to obtain extensive surface profiles of CLL cells obtained from 96 patients.
Of these 182 antigens, 27 were significantly differentially expressed between stable, stable-progressive and progressive CLL. Some of these antigens are not expressed on normal B-cells and may be targets for therapeutic antibodies against CLL. Unsupervised hierarchical clustering of the surface profiles from 96 patients showed that those with progressive CLL could be distinguished based solely upon this 'disease signature'. The sensitivity (proportion of actual positives correctly identified) was 67.9%, the specificity (proportion of negatives correctly identified) was 77.5%, and the accuracy was 71.9%.
Considerable effort by a number of research groups has resulted in identification of individual markers for progressive CLL, but their collective use is yet to provide a test that identifies CLL patients at risk. Data presented here provide a basis for development of a simple test using an antibody microarray.
慢性淋巴细胞白血病（CLL）是一种异质性疾病，一些患者可能会存活多年，而 20-30%的患者会进展，可能在数年内死亡。目前，没有单一的程序可以准确预测和分类那些需要立即进行积极治疗的患者。所有 CLL 细胞都表达 B 细胞抗原 CD19、CD20、CD21、CD22 和 CD23，同时异常表达 T 细胞抗原 CD5。
我们开发了一种含有 182 种固定化 CD 抗体的 CD 抗体微阵列（DotScan），已用于获得 96 例患者的 CLL 细胞的广泛表面图谱。
在这 182 个抗原中，有 27 个在稳定、稳定进展和进展性 CLL 之间存在显著差异表达。其中一些抗原不在正常 B 细胞上表达，可能是针对 CLL 的治疗性抗体的靶标。对 96 例患者的表面图谱进行无监督层次聚类分析显示，那些进展性 CLL 患者可以仅基于此“疾病特征”进行区分。敏感性（实际阳性的正确识别比例）为 67.9%，特异性（正确识别阴性的比例）为 77.5%，准确性为 71.9%。
许多研究小组进行了大量的努力，确定了进展性 CLL 的个别标志物，但它们的集体使用尚未提供一种可以识别有风险的 CLL 患者的测试。这里提供的数据为使用抗体微阵列开发简单测试提供了基础。
