Bone marrow mesenchymal stromal cells from acute myelogenous leukemiapatients exhibit aberrant gene expression profiles and secreted protein levels
Abstract Purpose: In hematopoietic malignancies, bone marrow mesenchymal stromal cells (BMSCs) are believed to promote tumor development through cellular and molecular abnormalities. However, there are several discrepancies among BMSCs in patients with acute myeloid leukemia (AML-MSCs) and healthy individuals (HD-MSCs) . Our aim was to analyze the differences in gene and protein levels between AML-MSCs and HD-MSCs, and to explore the role of AML-MSCs in the tumor microenvironment.Methods: We obtained MSCs from leukemia patients and healthy individuals and identified them by flow cytometry and differentiation. Transcriptome sequencing was performed on MSCs from leukemia patients and healthy individuals and label-free proteomics analysis was conducted on cultured supernatants of MSCs. Finally, we analyzed the results for bioinformatics analysis.Results: MSCs were preliminarily isolated and identified from AML patients and healthy controls. Through bioinformatics analysis, AML-MSCs and HD-MSCs showed great differences in Gene expression profiles and protein expression profiles of MSCs culture supernatants. Notably, inhibition of PI3K-Akt signal pathway can attenuate chemotherapy resistance of AML cells induced by MSC to AraC.Conclusions: Together, our findings suggest that Gene expression profiles and secreted protein levels of MSCs culture supernatants differed significantly between AML-MSCs and HD-MSCs, which should greatly facilitate the understanding of the role of MSCs in driving the development of acute myeloid leukemia and exploring new therapeutic strategies in future.