Function of the P2X7 receptor in hematopoiesis and leukemogenesis.

Abstract Adenosine triphosphate (ATP) accumulates at tissue injury and inflammation sites. The P2 × 7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, P2 × 7 receptors also play important roles in the growth of cancer and the immune regulation. Functional P2 × 7 receptor is widely expressed in murine and human hematopoietic stem cells and their lineages, including monocytes, macrophages, mast cells, and B or T lymphocytes, and participates in various physiological and pathological activities. Therefore, it is not surprising that the P2 × 7 receptor is important for the normal hematopoiesis and leukemogenesis. Here, we summarize the biological functions of P2 × 7 receptor during both normal hematopoiesis and leukemogenesis. In particular, we showed that ATP levels are dramatically increased in the leukemic bone marrow niche and the fates of leukemia-initiating cells of acute myeloid leukemia are tightly controlled by the P2 × 7 expression and ATP-P2 × 7-mediated signaling pathways. These findings strongly indicate that P2 × 7 receptor may be considered as a potential biomarker of hematological malignancies in bone marrow niches, and its antagonists may be useful for the leukemia treatment in addition to the traditional chemotherapy.