The myelodysplastic syndromes (MDS) are heterogeneous clonal disorders of ineffective hematopoiesis characterized by limited treatment options and a poor prognosis. These poor clinical characteristics stem from a poor understanding of the molecular abnormalities that drive disease pathogenesis. MicroRNAs (miRNAs) have recently been described to play wide-ranging roles in normal and malignant hematopoiesis, but very few miRNAs have been shown to be consistently dysregulated in MDS. Even fewer candidate disease miRNAs have undergone functional validation, and the clinical relevance of these miRNAs remains to be determined. Despite the fact that MDS has been shown to be a disease initiated in hematopoietic stem cells (HSC), most existing studies examining miRNA expression in MDS have used unfractionated or only partially purified bone marrow (BM) cell populations, likely explaining in part the limited insight that provided by these studies. A more robust characterization of purified disease -initiating cell populations followed by rigorous functional validation using in vivo disease models will be vital to identifying dysregulated miRNAs of functional significance in MDS. Such studies promise to provide key insights into disease pathogenesis and potentially open new avenues towards the development of therapies targeting miRNAs themselves or the pathways that they regulate.
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