De Marchi Elena, Pegoraro Anna, Adinolfi Elena
Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Front Cell Dev Biol. 2021 Mar 5;9:645605. doi: 10.3389/fcell.2021.645605. eCollection 2021.
The P2X7 receptor is an ion channel gated by the nucleotide ATP, known for its role in immune responses and recently emerging as a critical onco-promoting factor. Lymphocytes, myeloid cells, and their precursors were among the first cells proved to express a functional P2X7 receptor; therefore, it is not surprising that lymphoproliferative and myeloproliferative diseases, also known as hematological malignancies, were shown to be related in their insurgence and progression to P2X7 alterations. Here, we overview established and recent literature relating P2X7 with the biological mechanisms underlying leukemias, lymphomas, and multiple myeloma development. Particular attention is paid to studies published in the very recent past correlating P2X7 with ATP concentration in the leukemic microenvironment and P2X7 overexpression to acute myeloid leukemia aggressiveness and response to chemotherapy. The described literature strongly suggests that P2X7 and its genetic variants could be regarded as potential new biomarkers in hematological malignancies and that both P2X7 antagonists and agonists could emerge as new therapeutic tools alone or in combination with traditional chemotherapy.
P2X7受体是一种由核苷酸ATP门控的离子通道,因其在免疫反应中的作用而闻名,最近还成为一种关键的肿瘤促进因子。淋巴细胞、髓系细胞及其前体细胞是最早被证明表达功能性P2X7受体的细胞之一;因此,淋巴增殖性疾病和髓增殖性疾病,即血液系统恶性肿瘤,在其发生和发展过程中与P2X7改变相关也就不足为奇了。在此,我们概述了已有的和最新的文献,这些文献将P2X7与白血病、淋巴瘤和多发性骨髓瘤发生的生物学机制联系起来。特别关注最近发表的将P2X7与白血病微环境中的ATP浓度以及P2X7过表达与急性髓系白血病侵袭性和化疗反应相关联的研究。所述文献强烈表明,P2X7及其基因变体可被视为血液系统恶性肿瘤潜在的新生物标志物,并且P2X7拮抗剂和激动剂都可能单独或与传统化疗联合成为新的治疗工具。