Circulating MicroRNAs in Newly Diagnosed Acute and Chronic Leukemias

摘要

Leukemia is a clonal disease caused by genetic-epigenetic aberrations and we investigated the profile of circulating 741 microRNAs (miRNA) in plasma of newly diagnosed acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) patients compared to healthy individuals. MiRNAs are small non-coding RNA molecules and have critical roles in cell differentiation, proliferation, apoptosis. They regulate haematopoiesis in haematopoietic stem cells and committed progenitor cells, but they also play role in pathogenesis of acquired hematologic neoplasms. Recently, a growing body of evidence has implicated specific miRNAs in pathogenesis of leukemia and circulating miRNAs could serve as non-invasive biomarkers for detection of leukemia. Aim of this study was to identify miRNAs epigenetically regulated in acute and chronic leukemias. RNA was isolated using High Pure miRNA Isolation Kit (Roche) following manufacturer’s protocol. cDNA and preamplification protocols were obtained from isolated plasma miRNAs. The BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation) for real-time qPCR was used to simultaneously quantite the expression of 741 miRNAs. Statistical analyses were performed using Biogazelle’s qbase PLUS 2.0 software. Among analyzed 741 miRNAs, mir-1290 and miR-548c-3p were down-regulated, mir-24-3p, miR-30b- 5p and miR-19a-3p were up-regulated in all leukemic patients comparing with control group (p< 0.05). However, in patients with ALL, mir-24-3p was significantly down-regulated and miR-548c-3p was significantly up-regulated compared to healthy subjects (p< 0.05). Our study is the first study showing the higher expression levels of miR-548c-3p in ALL. We conclude that miR-24-3p and miR-548c-3p can be used as potential biomarkers for detecting ALL.