Purinergic Signaling in Stemness: The Potential Role of CD38 in Leukemia Development

Purinergic signaling is a critical pathway in cell-to-cell communication, influencing various cellular processes such as differentiation and self-renewal. Recent studies suggest that mesenchymal stem cells (MSCs) may contribute to the progression of tumors, potentially through purinergic signaling mechanisms. CD73 ectoenzyme, is a significant surface marker present on MSCs and plays a vital role in purinergic signaling by catalyzing the conversion of extracellular AMP to adenosine. The interaction of MSCs with surrounding cells, particularly within the bone marrow niche, raises important questions about their role in leukemic cell growth and drug resistance. Understanding the involvement of purinergic signaling in this context could provide insights into the early to late stages of hematological diseases, such as acute myeloid leukemia. This study utilized in vitro experimental models to explore the reciprocal regulation of mesenchymal stem cells and leukemia cells for the expression of CD73 (in MSCs) and CD45 (in KG-1). MSCs were co-cultured with KG-1 cells, assessing two different culture systems. To explore a possible regulation of the metabolic activity of leukemia cells, the mitochondrial content was explored by flow cytometry and data were correlated to the expression of the ectoenzyme CD38, that is reported to contribute to the activation of CD73 and the transfer of mitochondria between stromal and cancer cells. The cellular response of both MSCs and KG-1 was analyzed at three-time points (1,3, and 5 days). Preliminary results suggest that purinergic signaling may play a significant role in mediating the metabolic interactions between MSCs and KG-1 cells. These findings could potentially lay the foundation for further research into the therapeutic targeting of MSCs and the leukemia microenvironment in the development of leukemia.