Abstract
Myeloid malignancies, including myelodysplastic syndromes and acute myeloid leukemia, are clonal diseases arising in hematopoietic stem or progenitor cells. In recent years, microRNA (miRNA) expression profiling studies have revealed close associations of miRNAs with cytogenetic and molecular subtypes of myeloid malignancies, as well as outcome and prognosis of patients. However, the roles of miRNA deregulation in the pathogenesis of myeloid malignancies and how they cooperate with protein-coding gene variants in pathological mechanisms leading to the diseases have not yet been fully understood. In this review, we focus on recent insights into the role of miRNAs in the development and progression of myeloid malignant diseases and discuss the prospect that miRNAs may serve as a potential therapeutic target for leukemia.
Highlights
MicroRNAs are small non-coding RNAs with 19–22 nucleotides to control gene expression through binding to mRNA of their cognate target genes and thereby participate in numerous biological processes such as cell proliferation, differentiation, development, metabolism, apoptosis, survival, and hematopoiesis [1]. miRNA is transcribed by RNA pol II/III to generate a primary miRNA followed by nuclear cleavage by the RNase III endonuclease Drosha and its binding to the double-stranded RNA-binding protein DGCR8 to form a precursor miRNA [2, 3]
We focus on recent advances in understanding the roles of miRNA deregulation in the pathogenesis of myeloid malignancies and discuss the prospect that miRNAs may serve as potential therapeutic targets for leukemias
There are many more miRNAs, shown in publication, that are involved in the pathogenesis of myeloid malignancies, suggesting intense enthusiasm for research in this area in recent years
Summary
MicroRNAs are small non-coding RNAs with 19–22 nucleotides to control gene expression through binding to mRNA of their cognate target genes and thereby participate in numerous biological processes such as cell proliferation, differentiation, development, metabolism, apoptosis, survival, and hematopoiesis [1]. miRNA is transcribed by RNA pol II/III to generate a primary miRNA followed by nuclear cleavage by the RNase III endonuclease Drosha and its binding to the double-stranded RNA-binding protein DGCR8 to form a precursor miRNA (pre-miRNA) [2, 3]. We focus on recent advances in understanding the roles of miRNA deregulation in the pathogenesis of myeloid malignancies and discuss the prospect that miRNAs may serve as potential therapeutic targets for leukemias. Decreased expression of the miR-144/451 members targeting the erythroid transcription factor GATA-1 is closely associated with high-risk MDS [12, 49]. Overall, both the aberrant expression and the function of miRNAs are the important factors contributing to MDS pathogenesis and prognosis. Transgenic mice expressing hematopoietic miR-22 exhibit decreased global 5-hydroxymethylcytosine levels and increased HSC self-renewal along with defective differentiation and develop MDS and myeloid leukemia over time. A better understanding of miR-22 deregulation in MDS disease progression and AML transformation will provide insight into the mechanisms of MDS pathogenesis and provide new therapeutic strategies against leukemia transformation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
