Department of Hematology, University Tor Vergata, Roma.
Haematologica. 2012 Feb;97(2):279-87. doi: 10.3324/haematol.2011.052829. Epub 2011 Oct 11.
CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed.
We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators.
CD69 was associated with Rai stages (P=0.00002), β(2)-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69(+) plus ZAP-70(+) or CD38(+) or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of β(2)-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039).
Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization process.
CD69 在几种造血细胞中表达，是慢性淋巴细胞白血病的早期激活标志物。慢性淋巴细胞白血病是一种临床异质性疾病，需要易于管理的新的预后参数。
我们通过流式细胞术在 417 例慢性淋巴细胞白血病患者中研究了 CD69，并将其与其他生物学和临床预后指标进行了比较。
CD69 与 Rai 分期（P=0.00002）、β(2)-微球蛋白（P=0.0005）和可溶性 CD23（P<0.0001）相关。CD69 与 ZAP-70（P=0.018）或 CD38（P=0.00015）或免疫球蛋白可变重链基因突变（P=0.0005）也呈显著相关性。临床方面，CD69 阳性慢性淋巴细胞白血病更常接受化疗（74%；P<0.0001），并且在接受氟达拉滨联合利妥昔单抗治疗后反应持续时间更短（P=0.010），无进展生存期和总生存期也更短（P<0.0001）。CD69 具有真正的附加预后特性，因为 CD69(+) 加上 ZAP-70(+)或 CD38(+)或免疫球蛋白可变重链基因未突变的患者无进展生存期和总生存期最差（P<0.0001）。有趣的是，低 CD69 表达是预测β(2)-微球蛋白（P=0.002）、可溶性 CD23（P=0.020）或 Rai 分期 0-I（P=0.005）低肿瘤负荷患者更长无进展生存期所必需的。在无进展生存期和总生存期的多变量分析中，CD69 被确认为独立的预后因素（P=0.017 和 P=0.039）。
我们的数据表明，CD69 与不良的临床和生物学预后因素显著相关，并被证实为独立的疾病预后因素。这支持在适当的标准化过程后，将其引入常规实验室评估，并可能引入慢性淋巴细胞白血病的预后评分系统。
