東 剣虹
Department Research Institutes and Facilities, Research Institutes and Facilities Position Assistant Professor |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib. |
Journal | Formal name:International journal of molecular sciences Abbreviation:Int J Mol Sci ISSN code:(1422-0067)1422-0067(Linking) |
Volume, Issue, Page | 17(4),pp.570 |
Author and coauthor | Ohyashiki Kazuma, Umezu Tomohiro, Katagiri Seiichiro, Kobayashi Chiaki, Azuma Kenko, Tauchi Tetsuzo, Okabe Seiichi, Fukuoka Yutaka, Ohyashiki Junko H |
Publication date | 2016/04 |
Summary | Approximately 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. |
DOI | 10.3390/ijms17040570 |
PMID | 27092489 |