P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3.

Abstract

Nucleotides mediate intercellular communication by activating purinergic receptors and take part in various physiological and pathological processes. Abnormal purinergic signaling plays important roles in malignant progression. P2X7, which belongs to the P2X family of purinergic receptors, is abnormally expressed in various types of malignancies including leukemia. However, its role and molecular mechanism of action in leukemia have not been elucidated. Here, we analyzed the correlation between P2X7 expression and clinical outcome in acute myeloid leukemia (AML); we explored the role and mechanism of P2X7 in AML progression by using mouse AML, nude mouse xenograft and patientderived xenograft models. High levels of P2X7 expression were correlated with worse survival in AML. P2X7 was highly expressed in MLLrearranged AML and accelerated the progression of this type of AML both by promoting cell proliferation and by increasing leukemia stem cells. Furthermore, P2X7 caused upregulation of Pbx3 which might account for its pro-leukemic effects. The P2X7-Pbx3 pathway might also contribute to the progression of other types of leukemia as well as solid tumors with high levels of P2X7 expression. Our study provides new insights into the progression of malignancy caused by abnormal purinergic signaling.