Leukaemia: The Purinergic System and Small Extracellular Vesicles

Abstract

Haematopoiesis is a tightly regulated process, by intrinsic and extrinsic factors, to produce lifelong blood cell lineages within the bone marrow. In the bone marrow microenvironment, mesenchymal stem cells and haematopoietic stem cells play important roles to ensure that haematopoiesis is maintained. These cells contain purines and pyrimidines that control intercellular process such as energy transport. However, in some cases, this process may be misregulated thus leading to the production of various diseases, including leukaemia. As a result, bone marrow cells may be stimulated via stress or induced hypoxia, and this leads to the release of purine and pyrimidine nucleotides and nucleosides into the extracellular space, and activation of autocrine/paracrine feedback loops. These extracellular nucleotides and nucleosides, and their respective cell surface receptors are involved in purinergic signaling that control different physiologic functions in cells including proliferation, differentiation, and cell death. These extracellular nucleotides and nucleosides include ATP, UTP, adenosine diphosphate (ADP), UDP and adenosine however the most important players are ATP and its metabolite adenosine. ATP is degraded via a sequential activity of ectonucleotidases. ATP, adenosine and these ectonucleotidases play very important roles in the tumour microenvironment crucial to disease development, progression, and aggressiveness by modulating immune response to leukaemia treatment and increasing homing of leukaemic cells.