Acute myeloid leukemia cells and MSC-derived exosomes inhibiting transformation in myelodysplastic syndrome

Abstract

Abstract Aims To investigate the mechanism of exosomes role in the transformation of MDS to AML.Methods Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size and exosome surface marker proteins. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their effects on the proliferation, cycle, differentiation, apoptosis and cell microenvironment of MDS cell lines were analysed by CCK-8 assay and flow cytometry. Furthermore, exosomes from MSC were extracted for further authentication.RESULTS The transmission electron microscopy, nanoparticle tracking analysis, Western blotting and flow cytometry methods all showed that ultrafiltration is a reliable method for extracting exosomes. Exosomes from AML cell lines inhibit the proliferation of MDS cell lines, block cell cycle progression and promote apoptosis and cell differentiation. It also leads to increased secretion of tumour necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in MDS cell lines. In addition, MSC-derived exosomes were found to inhibit the proliferation of MDS cell lines, arrest cell cycle progression, promote apoptosis, and inhibit differentiation.CONCLUSION In this study, we explored that exosomes of AML cell line origin affect the apoptosis of MDS cell lines via the TNF-α/ROS-Caspase3 pathway, thereby influencing the conversion of MDS to AML. Additional, MSC-derived exosomes inhibited the transformation of MDS to AML.