miR-378-3p Knockdown Recapitulates Many of the Features of Myelodysplastic Syndromes
Cet article décrit le développement d'un modèle de maturation myéloïde aberrante reproduisant de nombreuses caractéristiques des syndromes myélodysplasiques
Myelodysplastic syndromes (MDS) are clonal neoplasms of the hematopoietic stem cell that result in aberrant differentiation of hematopoietic lineages due to a wide range of underlying genetic, epigenetic, and other causes. Despite the myriad etiologies, there is a recognizable MDS phenotype that has been associated with microRNA (miRNA) aberrant expression. A model of aberrant myeloid maturation mimicking MDS that is seen in MDS has been created using a stable knockdown of miR-378-3p. This model exhibited a transcriptional profile that indicates aberrant maturation and function, showed immunophenotypic and morphologic dysplasia, and displays the aberrant growth and function that characterizes MDS. Moreover, aberrant signal transduction in response to stimulation was demonstrated that is specific to the stage of myeloid maturation and mimics that seen in MDS patient samples using mass cytometry (CyTOF). The aberrant signaling, immunophenotypic changes, cellular growth, and colony formation ability seen in this myeloid model could be reversed with azacytidine (AZA) albeit without significant improvement of neutrophil function.
The American Journal of Pathology , résumé, 2020