Shaping Progress: Exploring the Impact of Human Bone Marrow Mesenchymal Stem Cell–Derived Exosomes on Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a type of cancer that arises from precursor cells in the myeloid lineage. Chromosomal translocations and mutations in genes controlling the proliferation and differentiation of hematopoietic cells lead to the buildup of immature myeloid cells in the bone marrow. AML is highly heterogeneous, classified into favorable, intermediate, and adverse-risk groups based on cytogenetic features, which significantly affect prognosis. Identifying recurrent genetic mutations has improved prognosis precision and treatment strategies. The bone microenvironment, particularly mesenchymal stem cells (MSCs) present in the stroma of the bone marrow, plays a critical role in AML progression and resistance to therapy. Recently, it has been shown that the repertoire of factors secreted by MSCs (called secretome) could be instrumental in modulating the expansion of AML cells and influencing local cellular responses to chemotherapeutics. Growth factors, cytokines, chemokines, extracellular matrix components, metabolic products, and most notably, exosomes, have all been recognized as functional molecules of MSCs. Exosomes released by BM-MSCs carry microRNAs and proteins that impact AML cells, influencing their viability (miR-23b-5p, miR-222-3p, and miR-7-5p) or providing resistance to chemotherapy (miR-10a and S100A4). Understanding the secretion and content of MSCs-exosomes is essential for unraveling the molecular pathways underlying leukemia development and progression. Moreover, it presents a promising avenue for the development of innovative therapeutic approaches in AML.