Abstract 1499: Expression and prognostic significance of microRNAs in Korean patients with myelodysplastic syndrome

Abstract

Abstract Introduction: MicroRNAs (miRNAs) are short non-coding RNAs that are involved in post-transcriptional regulation of gene expression, which may result in translational inhibition or destabilization of the target mRNA. Various alterations of miRNA expression have been reported in myelodysplastic syndrome (MDS). We aimed to investigate the unique patterns and prognostic significance of miRNA expression in Korean patients with MDS. Materials and Methods: Bone marrow mononuclear cells were collected from 10 healthy controls and 26 MDS patients, and miRNAs were isolated using a miRNeasy isolation kit (Qiagen) according to the manufacturer's instructions. Quantitative real-time PCR for selected miRNAs including miR-21, miR-124a, miR-126, miR-146b, miR-155, miR-200c, miR-342-5p, miR-708, and Let-7a was performed using a miScript SYBR green PCR kit (Qiagen). RNU6 was used to normalize the miRNA values of all RNA samples. Calculations were made using the comparative Ct (2-ΔΔCt ) method. Results: Eleven patients with early stage MDS (2 RA, 1 RARS, and 8 RCMD), 10 patients with advanced MDS (3 RAEB-1 and 7 RAEB-2), 4 patients with unknown subtype of MDS, and 1 patient with chronic myelomonocytic leukemia were included in this study. Median age was 58.5 years (range, 13-76). MiR-124a, miR-155, miR-200c, miR-342-5p, and let-7a were significantly under-expressed in MDS patients compared to healthy controls. Levels of miR-124, miR-146b, and miR-155 transcripts were significantly lower in patients with early stage MDS than in those with advanced MDS. Secondary MDS patients (n=6) showed significantly under-expressed MiR-146b and miR-342-5p transcript levels than de novo MDS patients (n=19) (p=0.009 and p=0.043, respectively). We failed to find statistically significant survival differences according to the expression levels of miRNAs, although high expression of miR-124, miR-126, miR-155 and low expression of miR-342-5p tended to be associated with poor overall survival and leukemia free survival. Conclusion: We first report under-expression of miR-200c in MDS patients. Expression of miRNAs appears to be different according to the stage of MDS. Further investigations are needed to evaluate genetic functions and prognostic significances of miRNAs in MDS. Citation Format: Yunsuk Choi, Eun-Hye Hur, Ju Hyun Moon, Bon-Kwan Goo, Dae Ro Choi, Je-Hwan Lee. Expression and prognostic significance of microRNAs in Korean patients with myelodysplastic syndrome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1499. doi:10.1158/1538-7445.AM2014-1499