Prognostic significance of toll-like receptors 2/4 expression ratio in chronic lymphocytic leukemia

Background Chronic lymphocytic leukemia (CLL) is the most common lymphoid malignancy in adults. Toll-like receptors (TLRs) represent a family of essential immune biomolecules. In this work, we aimed to assess the prognostic value of the levels of both TLR2 and TLR4 repressed as TRL2/4 ratio in CLL patients. Patients and methods The study included 50 newly diagnosed CLL patients and 20 age and sex matched healthy controls. Patients were followed for a median (range) eight (1–18) months. Outcome parameters included (1) treatment response classified as complete response, partial response or no response, (2) progression free survival (PFS) and (3) overall survival. Results The studied patients had TLR2 expression level of median (interquartile range): 6.4 (6.1–6.6), TLR4 expression level of 2.6 (2.3–3.0) and TLR2/4 ratio of 2.18 (0.085–2.67). Patients had significantly higher TLR2, and higher TLR2/4 ratio when compared with controls. Patients were classified according to those with low TLR2/4 ratio (≤median) or high TLR2/4 ratio (>median). Patients with low TLR2/4 ratio had significantly higher frequency of relapses (26.7% vs. 5.7%, P =0.037) and nonsurvivors (60.0% vs. 11.4%, P <0.001) Patients with low TLR2/4 ratio had significantly shorter PFS [mean (95% CI): 10.3 (7.5–13.2) vs. 14.4 (12.0–16.7) months, P =0.018] and overall survival [mean (95% CI): 12.0 (9.1–14.9) vs. 15.7 (13.7–17.7) months, P 0.021]. Univariate cox-hazard regression analysis identified low TLR2/4 as significant predictor of PFS [HR (95% CI): 0.23 (0.07–0.81), P =0.022]. Conclusions TLR2/4 ratio may be a valid prognostic marker in CLL patients.