MicroRNA expression profiling as supportive diagnostic and therapy prediction tool in chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cells carrying Philadelphia (Ph) chromosome and the oncogenic BCR-ABL1 fusion gene. microRNAs (miRNAs) belong to hematopoiesis transcription regulators and their deregulated expression associates with pathogenesis of CML. The current study assesses and validates expression profiles of selected oncogenic and tumor suppressing miRNAs that are associated with different imatinib mesylate (IM) response in CML patients carrying rare BCR-ABL variants. Microarray analysis has identified different expression of 70 miRNAs (46 up- and 24 down-regulated) when compared IM-resistant with IM-responsive patients carrying Ph chromosome. Significantly up-regulated expression of oncogenic miRNAs (miR-17, miR-18a, miR-20a, miR-21, miR-27a and miR-155) and significantly down-regulated expression of tumor supressing mRNAs (let-7d, miR-205, miR-320, miR-451 and miR-574) in IM-resistant compared to IM-responsive patients was confirmed and validated by qRT-PCR. This study confirms the involvement of the selected oncogenic and tumor suppressing miRNAs in CML pathogenesis and IM response and suggests that these miRNAs could be suitable biomarkers for differential diagnosis of CML patients carrying rare BCR-ABL transcripts, as well as for prediction of their IM response and therapy outcome.