TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia

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.