Antigenic stimulation is considered as a possible trigger of neoplastic transformation in chronic lymphocytic leukemia (CLL). B-cell receptor plays a key role in the interactions between the microenvironment and leukemic cells; however, an important role has also been attributed to Toll-like receptors (TLRs). It is believed that disorders of TLR expression may play a part in the pathogenesis of CLL. In this study, we investigated the potential role of TLR2 in CLL by analyzing its expression on leukemic B cells in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. We assessed the frequencies of TLR2+/CD19+ cells by the flow cytometry method in peripheral blood of 119 patients with CLL. The percentage of TLR2+/CD19+ cells was significantly lower in patients with CLL as compared to the healthy volunteers. There was also a lower percentage of TLR2+/CD19+ cells in CLL patients with poor prognostic factors, such as ZAP70 and/or CD38 expression, 17p and/or 11q deletion. On the other hand, among patients with del(13q14) associated with favorable prognosis, the percentage of TLR2+/CD19+ cells was higher than among those with del(11q22) and/or del(17p13) as well as in the control group. We found an association between low percentage of CD19+/CD5+/TLR2+ cells and shorter time to treatment. We also demonstrated the relationship between low percentage of CD19+/CD5+ TLR2-positive and overall survival (OS) of CLL patients. CLL patients with a proportion of 1.6% TLR2-positive B CD5+ cells (according to the receiver operating characteristic curve analysis) or more had a longer time to treatment and longer OS than the group with a lower percentage of TLR2 positive cells. To sum up, the results of the study suggest that low TLR2 expression is associated with poor prognosis in CLL patients. The monitoring of CD19+/CD5+/TLR2+ cells number may provide useful information on disease activity. Level of TLR2 expression on leukemic B cells may be an important factor of immunological dysfunction for patients with CLL. Our study suggests that TLR2 could becomes potential biological markers for the clinical outcome in patients with CLL.

中文翻译：

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慢性淋巴细胞性白血病患者白血病B细胞上TLR2的表达。

抗原刺激被认为是慢性淋巴细胞性白血病（CLL）肿瘤转化的可能诱因。B细胞受体在微环境与白血病细胞之间的相互作用中起着关键作用。然而，重要的作用也归因于Toll样受体（TLR）。相信TLR表达的异常可能在CLL的发病机理中起作用。在这项研究中，我们通过分析TLR2在白血病B细胞中的表达与表征疾病活动性和患者免疫状况的临床和实验室参数的相关性，研究了TLR2在CLL中的潜在作用。我们通过流式细胞术评估了119例CLL患者外周血中TLR2 + / CD19 +细胞的频率。与健康志愿者相比，CLL患者中TLR2 + / CD19 +细胞的百分比显着降低。在具有不良预后因素（例如ZAP70和/或CD38表达，17p和/或11q缺失）的CLL患者中，TLR2 + / CD19 +细胞的百分比也较低。另一方面，在del（13q14）患者预后良好的患者中，TLR2 + / CD19 +细胞的百分比高于del（11q22）和/或del（17p13）患者以及对照组。我们发现低百分比的CD19 + / CD5 + / TLR2 +细胞与更短的治疗时间之间存在关联。我们还证明了低水平的CD19 + / CD5 + TLR2阳性率与CLL患者的总生存期（OS）之间的关系。CLL患者的比例为1。相对于TLR2阳性细胞百分比较低的组，6％或更高的TLR2阳性B CD5 +细胞（根据接受者的工作特征曲线分析）具有更长的治疗时间和更长的OS。综上所述，该研究结果表明，TLR2的低表达与CLL患者的预后不良有关。CD19 + / CD5 + / TLR2 +细胞数量的监测可能会提供有关疾病活动的有用信息。白血病B细胞上TLR2表达的水平可能是CLL患者免疫功能异常的重要因素。我们的研究表明，TLR2可能成为CLL患者临床预后的潜在生物学标记。研究结果表明，TLR2的低表达与CLL患者的预后不良有关。CD19 + / CD5 + / TLR2 +细胞数量的监测可能会提供有关疾病活动的有用信息。白血病B细胞上TLR2表达的水平可能是CLL患者免疫功能异常的重要因素。我们的研究表明，TLR2可能成为CLL患者临床预后的潜在生物学标记。研究结果表明，TLR2的低表达与CLL患者的预后不良有关。CD19 + / CD5 + / TLR2 +细胞数量的监测可能会提供有关疾病活动的有用信息。白血病B细胞上TLR2表达的水平可能是CLL患者免疫功能异常的重要因素。我们的研究表明，TLR2可能成为CLL患者临床预后的潜在生物学标记。