Identification of nilotinib-altered microRNA expression patterns in imatinib-resistant chronic myeloid leukemia cells

Abstract

Drug resistance is a key contributor for treatment failure in hematologic and other malignancies. Nilotinib has been observed with significant activity in patients with chronic phase chronic myeloid leukemia (CML) who have failed or are intolerant of imatinib therapy. Recent reports have suggested that microRNA (miRNA) expression changes are involved in the drug response of human cancer. Several miRNAs have been previously found to be consistently deregulated in imatinib resistance; however, very limited information is available for nilotinib-treated patients who have failed imatinib therapy. Many reports have discovered circulating miRNAs as noninvasive biomarkers of disease and therapy response. The aim of this study was to explore miRNA regulation and find candidate miRNA markers for CML that can be used for drug response prediction. Here we demonstrate the circulating miRNA profile in the culture supernatant of imatinib-resistant K562 CML cells (K562-R) by microarray chip analysis. We have identified specific miRNAs that are associated with nilotinib sensitivity by comparison of miRNA expression patterns from the culture supernatant of nilotinib-treated K562-R cells with the culture supernatant of untreated K562-R cells. The information obtained from this study may have the potential to become a novel biomarker to predict drug response in the future and can also be applied to developing novel therapeutic treatment for CML.