Acute myeloid leukaemia:analysis of the expression of P2X7a and P2X7B isoforms

Acute Myeloid Leukaemia (AML) is a clonal disorder originating from the accumulation of myeloid progenitor cells in the bone marrow. An increasing number of reports correlate P2X7 with tumor growth and progression (Adinolfi et al. 2015). Haemopoietic lympho-proliferative disorders, among which AML (Salvestrini et al. 2012) were the first neoplastic models where P2X7 oncopromoting activity was demonstrated (Adinolfi et al., 2002; Chong et al., 2010).The P2X7 receptor for extracellular ATP is a ionotropic, ligand-gated, cation channel and it is expressed by different cell types such as neurons, macrophages, dendritic and microglial cells, fibroblasts, endothelial cells and lymphocytes. Nine different P2X7 splice variants have been detected in humans, among those just two, P2X7A and P2X7B are functional ion channels (Cheewatrakoolpong et al., 2005) both showing growth promoting activity (Adinolfi et al., 2010; Giuliani et al., 2014). Isoform B is a naturally truncated P2X7 splice variant, widely expressed in several human tissues especially in lymphoid tissue and lymphocytes themselves, often to a much higher level than P2X7A. Considering that a wide characterization of P2X7B is still lacking, we analyzed the differential expression of P2X7A and P2X7B in a cohort of AML patients by Real Time PCR. We obtained a significant correlation between high P2X7B expression and relapse as compared to onset of disease. Moreover, low P2X7A expression associates with favorable karyotype and, although not significant, there is a similar tendency for P2X7B. Futhermore, preliminary data suggest a correlation between age of onset (>65 years) and high P2X7B expression. Although a wider cohort analysis will be required, these data prompt us to postulate that different P2X7A and B expression levels could be involved in AML development, suggesting that P2X7 could be a valuable prognostic marker and therapeutic target for the disease.