The role of IL-17/IL-6 axis in the development of chronic lymphocytic leukemia.
2015
e22119 Background: The tumor microenvironment (TME) is critical to the survival of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produced are important components of TME. Methods: 49 Patients with various stages of CLL were included. BMMSCs were co-cultured with human CLL cells with or without the presence of IL-17. Peripheral blood mononuclear cells from CLL patients were injected into NSG mice and IL-6/IL-17 were delivered daily. Student t test and Pearson product-moment correlation were used in statistical analysis. Results: CLL cells survived better when co-cultured with BMMSCs. ELISA array revealed a high concentration of IL-6 in co-culture system. Inhibition of IL-6 by Actemra decreased CLL cell survival in the co-culture. IL-6 production can be induced by IL-17 in both BMMSCs and CLL cells. In a xenograft animal model, BMMSCs and its culture supernatant promoted the engraftment of CLL cells via inducing IL-6. Human recombinan...
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