Downregulation of extracellular vesicle microRNA‑101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression

Abstract

To evaluate the mechanism underlying the communication between myeloid malignant and bone marrow (BM) microenvironment cells in disease progression, the current study established BM mesenchymal stromal cells (MSCs) and assessed extracellular vesicle (EV) microRNA (miR) expression in 22 patients with myelodysplastic syndrome (MDS) and 7 patients with acute myeloid leukemia and myelodysplasia-related changes (AML/MRC). Patients with MDS were separated into two categories based on the revised International Prognostic Scoring System (IPSS-R), and EV-miR expression in BM-MSCs was evaluated using a TaqMan low-density array. The selected miRs were evaluated using reverse transcription-quantitative PCR. The current study demonstrated that the expression of BM-MSC-derived EV-miR was heterogenous and based on MDS severity, the expression of EV-miR-101 was lower in high-risk group and patients with AML/MRC compared with the control and low-risk groups. This reversibly correlated with BM blast percentage, with which the cellular miR-101 from BM-MSCs or serum EV-miR-101 expression exhibited no association. Database analyses indicated that miR-101 negatively regulated cell proliferation and epigenetic gene expression. The downregulation of BM-MSC-derived EV-miR-101 may be associated with cell-to-cell communication and may accelerate the malignant process in MDS cells.

Extracellular Vesicles in Myeloid Neoplasms

“…The authors also showed that these EVs could be taken up by healthy CD34+ cells inducing alterations in the expression of MDM2 and TP53 in these cells and in their clonogenicity [ 118 ]. It was also reported that the expression of miR-101 was downregulated in EVs derived from mesenchymal stromal cells from patients with high-risk MDS and acute myeloid leukemia compared to patients with low-risk disease [ 119 ]. Of note, miR-101 suppresses cell proliferation [ 119 ] suggesting that its downregulation could be implicated in the acceleration of MDS cell proliferation and transformation to acute leukemia.…”

“…It was also reported that the expression of miR-101 was downregulated in EVs derived from mesenchymal stromal cells from patients with high-risk MDS and acute myeloid leukemia compared to patients with low-risk disease [ 119 ]. Of note, miR-101 suppresses cell proliferation [ 119 ] suggesting that its downregulation could be implicated in the acceleration of MDS cell proliferation and transformation to acute leukemia. Finally, Meunier et al recently found that small EVs from mesenchymal stromal cells derived from MDS patients induce ROS production promoting DNA damage and mutagenesis in healthy HSC via miRNA transfer [ 120 ].…”

Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma

“…A prognostic significance of EV-microRNAs has also been confirmed in several other hematological malignancies. Saito et al observed a different EV-microRNA expression in subjects with myelodysplastic syndrome and acute myeloid leukemia during disease progression [ 119 ]. EVs might also have a prominent role in MM onset and progression by controlling endothelial cell functions, augmenting tumor cell growth, and increasing immunosuppression [ 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 ].…”