DICER1 gene and miRNA dysregulation in mesenchymal stem cells of patients with myelodysplastic syndrome and acute myeloblastic leukemia

Multipotent mesenchymal stem cells (MSC) are key components of the bone marrow (BM) microenvironment. The contribution of this microenvironment to the pathophysiology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is not well defined. A recent study in mice demonstrated that DICER1 gene deletion in osteoprogenitor cells from the BM microenvironment suppressed osteogenic differentiation and induced MDS and AML-like haematological findings. The present study evaluated the expression profiles of microRNAs (miRNAs) and DICER1 gene in BM-derived MSC of patients with AML (n= 12), MDS (n = 10) and healthy controls (HC) (n= 8). miRNA expression profiles were analyzed by microarray and confirmations were performed using quantitative real-time PCR (qRT-PCR). Patient MSC displayed impaired proliferative and differentiation potential compared to HC. DICER1 gene expression was lower in MSC from MDS and AML patients than HC and some differentially expressed miRNAs indicated the potential involvement of DICER1 in the pathogenesis of MDS and AML. qRT-PCR confirmation revealed down-regulated miRNAs (hsa-miR-30d-5p, hsamiR- 222-3p and hsa-miR-30a-3p in MDS; hsa-miR-1275, hsa-miR-4725-5p and hsa-miR-143-3p in AML) and over-expressed miRNAs (hsa-miR-4462 in MDS; hsa-miR-134-5p and hsa-miR-874-3p in AML) in MDS and AML. Thus, our findings validate the results of the aforementioned animal study and demonstrate downregulation of DICER1 gene and abnormal miRNA profile in MDS and AML, which may have implications for understanding MDS and AML pathogenesis and contribute to developing targeted treatment strategies.