FIGURE 2.

Canonical and noncanonical pathways of adenosine production in normal conditions and in the hypoxic MM BM niche. This figure shows the shift to noncanonical pathway of ADO production in the presence of a low pH environment, such as in the BM niche. An excess of NAD⁺ due to the shift from oxidative phosphorylation to aerobic glycolysis activates the CD38/CD203a/TRACP pathway, while the low pH also causes the inhibition of CD73. Additionally, ATP can be directly converted to AMP by CD203a. ADO, adenosine; ADP, adenosine diphosphate; ADPR, adenosine diphosphate ribose; AMP, adenosine monophosphate; ATP, adenosine triphosphate; CD203a, ectonucleotide pyrophosphatase/phosphodiesterase‐1; CD38, cyclic ADP‐ribose hydrolase; CD39, ectonucleoside triphosphate diphosphohydrolase‐1; CD73, 5′ nucleotidase; TRACP, tartrate‐resistant acid phosphatase.