Assessment of soluble cytotoxic T lymphocyte-associated antigen-4, transforming growth factor β1, and platelet-derived microparticles during dasatinib therapy for patients with chronic myelogenous leukemia

Shosaku Nomura, Tomoki Ito, Atsushi Satake, Kazuyoshi Ishii First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, Japan Background: The outcome for chronic myelogenous leukemia (CML) patients presented in the chronic phase has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. Notably, an increased incidence of large granular lymphocytes (LGLs), which is related to immunological conditions, appears to be predictive of a favorable outcome for dasatinib therapy. We therefore examined the immunological characteristics of CML patients during dasatinib therapy by determining the plasma concentrations of five different biomarkers. Methods: The plasma levels of biomarkers, specifically interleukin-6, platelet-derived microparticles (PDMPs), soluble vascular cell adhesion molecule 1 (sVCAM-1), transforming growth factor (TGF) β1, and soluble cytotoxic T lymphocyte-associated antigen-4 (sCTLA-4), were measured by ELISA at baseline and after 2 and 6 months of TKI treatment. The incidence of LGLs was estimated by microscopic examination. Results: The levels of PDMPs, sVCAM-1, and TGFβ1 were significantly elevated in patients with CML. Dasatinib treatment was associated with a significant reduction in the levels of these markers and with an increased incidence of LGLs compared with imatinib or nilotinib treatment. In addition, an increased incidence of LGLs was significantly correlated with a decreased sCTLA-4 level during dasatinib therapy. Conclusion: The assessment of the levels of specific biomarkers may be beneficial to understand the immunological conditions of patients with CML during dasatinib treatment. Keywords: CML, TKI, LGL, PDMP, TGFβ1, sCTLA-