Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients

SIMPLE SUMMARY: Tie2-expressing monocytes (TEM) characterized by the phenotype of CD14+CD16+Tie2+ are seen as the new immunosuppressive force in tumors. However, little is known about the role of circulating TEM in chronic lymphocytic leukemia (CLL) as opposed to their role in solid tumors. In the current study, we observed an increased percentage of TEMs in CLL patients. A greater than 14.82% proportion of TEM foretells an unfavorable prognosis. This threshold has predicted a shorter time from diagnosis to therapy, and worse overall survival. Despite these results, a multivariable Cox regression model performed in 104 CLL patients did not identify TEM as an independent predictor of survival. However, TEM, as an important element of the tumor-microenvironment, can be an important complement to other prognostic indicators. ABSTRACT: Tie2-expressing monocytes (TEMs) are associated with tumor progression and metastasis. This unique subset of monocytes has been identified as a potential prognostic marker in several solid tumors. However, TEMs remain poorly characterized in hematological cancers, including chronic lymphocytic leukemia (CLL). This study analyzed, for the first time, the clinical significance of TEM population in CLL patients. Flow cytometry analysis of TEMs (defined as CD14(+)CD16(+)Tie2(+) cells) was performed at the time of diagnosis on peripheral blood mononuclear cells from 104 untreated CLL patients. Our results revealed an expansion of circulating TEM in CLL patients. These monocytes express high levels of VEGF and suppressive IL-10. A high percentage of TEM was associated closely with unfavorable prognostic markers (ZAP-70, CD38, 17p and 11q deletion, and IGHV mutational status). Moreover, increased percentages of circulating TEMs were significantly higher in patients not responding to the first-line therapy as compared to responding patients, suggesting its potential predictive value. High TEM percentage was also correlated with shorter overall survival (OS) and shorter time to treatment (TTT). Importantly, based on multivariate Cox regression analysis, TEM percentage was an independent predictor for TTT. Thus, we can suggest the adverse role of TEMs in CLL.