Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib
AbstractApproximately 40% of chronic myeloid leukemia (CML) patients who discontinue imatinib (IM) therapy maintain undetectable minimal residual disease (UMRD) for more than one year (stopping IM (STOP-IM)). To determine a possible biomarker for STOP-IM CML, we examined plasma miRNA expression in CML patients who were able to discontinue IM. We first screened candidate miRNAs in unselected STOP-IM patients, who had sustained UMRD after discontinuing IM for more than six months, in comparison with healthy volunteers, by using a TaqMan low-density array for plasma or exosomes. Exosomal miR-215 and plasma miR-215 were downregulated in the STOP-IM group compared to the control, indicating that the biological relevance of the plasma miR-215 level is equivalent to that of the exosomal level. Next, we performed real-time quantitative RT-PCR in 20 STOP-IM patients, 32 patients with UMRD on continued IM therapy (IM group) and 28 healthy volunteers. The plasma miRNA-215 level was significantly downregulated in the STOP-IM group (p < 0.0001); we determined the cut-off level and divided the IM group patients into two groups according to whether the plasma miR-215 was downregulated or not. The IM group patients with a low plasma miR-215 level had a significantly higher total IM intake, compared to the patients with elevated miR-215 levels (p = 0.0229). Functional annotation of miR-215 target genes estimated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatic tools involved cell cycle, mitosis, DNA repair and cell cycle checkpoint. Our study suggests a possible role of miR-215 in successful IM discontinuation. View Full-Text
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Ohyashiki, K.; Umezu, T.; Katagiri, S.; Kobayashi, C.; Azuma, K.; Tauchi, T.; Okabe, S.; Fukuoka, Y.; Ohyashiki, J.H. Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib. Int. J. Mol. Sci. 2016, 17, 570.
Ohyashiki K, Umezu T, Katagiri S, Kobayashi C, Azuma K, Tauchi T, Okabe S, Fukuoka Y, Ohyashiki JH. Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib. International Journal of Molecular Sciences. 2016; 17(4):570.Chicago/Turabian Style
Ohyashiki, Kazuma; Umezu, Tomohiro; Katagiri, Seiichiro; Kobayashi, Chiaki; Azuma, Kenko; Tauchi, Tetsuzo; Okabe, Seiichi; Fukuoka, Yutaka; Ohyashiki, Junko H. 2016. "Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib." Int. J. Mol. Sci. 17, no. 4: 570.
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