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

Agata Szymańska,Jacek Roliński,Waldemar Tomczak,Arkadiusz Drobiecki,Marek Hus,Agnieszka Bojarska-Junak,Iwona Hus

doi:10.1007/s00005-018-0523-9

Abstract

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.

Highlights

Chronic lymphocytic leukemia (CLL) is characterized by the proliferation and accumulation of clonal B cells in bone marrow, peripheral blood, lymph nodes, spleen and more rarely extralymphatic organs
Significant differences in the percentages of CD19+/CD5+/ TLR2+ cells were noted in patients with CLL depending on the presence of poor prognostic factors
No significant differences were observed in the percentage of CD19+/CD5+/TLR2+ (median: CLL 0.38%; healthy volunteers (HV) 1.58%) and CD19+/CD5−/TLR2+ (p > 0.05)

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is characterized by the proliferation and accumulation of clonal B cells in bone marrow, peripheral blood, lymph nodes, spleen and more rarely extralymphatic organs. TLRs are transmembrane proteins present on the surface and in endosomes of many cell types Their stimulation influences the induction of the innate immune system, with particular importance of TLRs expressed on antigen-presenting cells (APC; dendritic cells, mast cells, macrophages and B cells) (Dajon et al 2017; Meyer-Bahlburg and Rawlings 2008). Stimulation of TLR2 on C D4+CD25+ regulatory T (Treg) cells by PAMP induces increased IL-10 release, leading to suppression of both humoral and cell-mediated immunity. This results in decreasing of Treg suppressor properties (Guangwei and Yong 2007; Netea et al 2004)

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