Involvement of A-to-I RNA editing in myeloid cell commitment and differentiation

Post-transcriptional modification events, such as RNA editing, are emerging as new players in several human diseases, including cancer. A-to-I RNA editing changes the nucleotide sequence of target RNAs, introducing A-to-I/G “mutations”. Thus, it is not surprising that alterations in both ADAR expression and activity are present in several human cancers. However, only recently a mechanicistic connection between a specific editing on RNA target genes and cancer has been proven. Of note, studies in mice showed that ADAR1 was required for normal hematopoiesis and for promoting malignant progenitor reprogramming in chronic myeloid leukemia. My project was focused on the analysis of ADAR1 in the maturation of leukemia cell lines compared to peripheral blood mononuclear cells. We analyzed the expression of ADAR1 enzyme and editing activity at specific substrates in two monocytic leukemia cell lines (U937 and THP-1) as well as in perypheral blood monocytes from healthy donors, undergoing differentiation to a mature phenotype by different stimuli (PMA, GM-CSF, GMCSF plus Vitamin D3). RNA sequence analysis and validation of the targets of the ADAR1 activity have provided some relevant informations about the role of the RNA editing in the maturation/differentiation of myeloid cells.