Targeting the tumor promoting effects of adenosine in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms. In this review, we focused on the multiple functions and related mechanisms of ADO signaling in CLL generation and progression.