TY - JOUR
T1 - MicroRNA dysregulation in the myelodysplastic syndromes
AU - Chung, Stephen S.
AU - Park, Christopher Y.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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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U2 - 10.2174/2211536602666131126002621
DO - 10.2174/2211536602666131126002621
M3 - Review article
C2 - 25069441
AN - SCOPUS:85013886955
SN - 2211-5366
VL - 2
SP - 174
EP - 186
JO - MicroRNA (Shariqah, United Arab Emirates)
JF - MicroRNA (Shariqah, United Arab Emirates)
IS - 3
ER -