Myelodysplastic Stem Cells: Gene Expression Profiling

Myelodysplastic syndromes (MDS) represent a group of diseases associated with bone marrow failure arising from the interaction between a clonal and deranged hematopoietic stem cell (HSC) and a deregulated bone marrow microenvironment. Several abnormalities have been described in the development of myelodysplastic stem cells which give origin to dysplastic hematopoiesis, including increased apoptosis, decreased survival, depletion of early hematopoietic cells and abnormal differentiation. Gene expression profiling (GEP) studies have allowed a clear discrimination between normal and myelodysplastic HSCs. Moreover, distinct gene expression signatures have been associated with disease stage (early versus advanced), prognosis, morphology and presence of recurrent chromosomal abnormalities, such as monosomy 7/deletion 7q, trisomy 8 and deletion 5q. Most interestingly, GEP has allowed the identification of crucial genes and biologic pathways deranged in MDS including among all interferon signaling, ribosomal protein biogenesis, immune response, Wnt/ β-catenin signalling, cell cycle control and DNA damage response. These pathways beside shedding light on the comprehension of MDS pathobiology, may represent the basis for further investigations and realization of a more targeted approach in the therapeutic management of these diseases. Strictly correlated to GEP, miRNA profiling identified distinct miRNAs deregulated in MDS, which can significantly influence expression of coding transcripts in myelodysplastic stem cells.