An Analysis of MicroRNA Expression in the Myelodysplastic Syndromes Using Hematopoietic Stem Cells
Technical Report,15 Jul 2013,14 Jul 2015
Sloan Kettering Institute for Cancer Research New York United States
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We utilized primary bone marrow specimens from patients with the myelodysplastic syndromes MDS to identify microRNAs miRNAs dysregulated in MDS hematopoietic stem cells MDS HSCs as compared with normal HSCs. MiRNAs differentially expressed between MDS HSCs and normal HSCs overlapped significantly with those differentially expressed between HSCs from old and young normal patients, suggesting that MDS pathogenesis may overlap significantly with that of normal aging. A miRNA significantly downregulated in normal older HSCs that was further downregulated in MDS was miR-125b. We examined old and young mice to confirm that miR-125b is also downregulated in older mice, and studies reintroducing miR-125b into old HSCs restored their long-term reconstitution capacity and self-renewal as demonstrated by serial transplantation assays. Together, these findings validate the functional role of miR-125b in hematopoiesis in the context of aging and its likely implication in the age-related predisposition for the development of MDS.