P2X7 receptor: An emerging therapeutic target in acute myeloid leukemia (Review)

The P2X7 receptor (P2X7R) is a ligand‑gated ion channel that exhibits bifunctional properties, switching between a cation‑permeable channel and a large cytolytic pore. In acute myeloid leukemia (AML), P2X7R is aberrantly overexpressed, particularly in leukemia stem cells (LSCs) and AML blasts. Within the bone marrow niche of AML, P2X7R binding by extracellular adenosine triphosphate not only contributes to a profound immunosuppressive niche that protects the AML cells from immune surveillance, but also drives LSC proliferation, survival, homing, and self‑renewal through downstream signaling cascades, including the cAMP response element‑binding protein/phosphoglycerate dehydrogenase/serine metabolic axis, PBX homeobox 3, Wnt/β‑catenin, and c‑Myc. Elevated P2X7R expression is associated with poor prognosis, chemoresistance, and disease recurrence of AML. The central role of P2X7R in AML pathophysiology makes it a potential biomarker for prognostic stratification and a promising therapeutic target. Several targeting strategies are currently under investigation, including the small molecule antagonists and specific anti‑P2X7R antibodies. Furthermore, a therapeutic approach involves combining P2X7R inhibition with conventional chemotherapy. In conclusion, targeting the P2X7R pathway represents a potential novel and multi‑faceted strategy to improve outcomes for patients with AML by remodeling its protective microenvironment and directly attacking the leukemia cells.