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 syndromesMDS to identify microRNAs miRNAs dysregulated in MDS hematopoietic stem cells MDS HSCsas compared with normal HSCs. MiRNAs differentially expressed between MDS HSCs and normalHSCs overlapped significantly with those differentially expressed between HSCs from old andyoung normal patients, suggesting that MDS pathogenesis may overlap significantly with thatof normal aging. A miRNA significantly downregulated in normal older HSCs that was furtherdownregulated in MDS was miR-125b. We examined old and young mice to confirm that miR-125b isalso downregulated in older mice, and studies reintroducing miR-125b into old HSCs restoredtheir long-term reconstitution capacity and self-renewal as demonstrated by serialtransplantation assays. Together, these findings validate the functional role of miR-125b inhematopoiesis in the context of aging and its likely implication in the age-relatedpredisposition for the development of MDS.