Figure 2.

ADO in the chronic lymphocytic leukemia (CLL) lymphoid niche is part of a complex network of micro-environmental signals. The CLL niche is a hypoxic environment, as witnessed by high levels of HIF1α compared to reactive lymph nodes (LN) from healthy individuals. HIF1α modulates the adenosinergic axis both in bystander and CLL cells. These populations expressed on their cell surface the enzymatic machinery to dismantle ATP/ADP/AMP, generating ADO. This nucleoside can exert paracrine or autocrine effects, mediated at least in part through the binding to A2A receptor, or can be dismantled to inosine.