{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:27:40Z","timestamp":1776457660585,"version":"3.51.2"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms17040570","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T11:36:02Z","timestamp":1460720162000},"page":"570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-5758","authenticated-orcid":false,"given":"Kazuma","family":"Ohyashiki","sequence":"first","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 160-0023, Japan"},{"name":"Department of Molecular Science, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-8921","authenticated-orcid":false,"given":"Tomohiro","family":"Umezu","sequence":"additional","affiliation":[{"name":"Department of Molecular Science, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-9990","authenticated-orcid":false,"given":"Seiichiro","family":"Katagiri","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Science, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenko","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuzo","family":"Tauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichi","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Kogakuin University, Tokyo 163-8677, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Ohyashiki","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/leu.2009.38","article-title":"Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia","volume":"23","author":"Hochhaus","year":"2009","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1182\/blood-2013-05-501569","article-title":"European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013","volume":"122","author":"Baccarani","year":"2013","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Intergroupe Fran\u00e7ais des Leuc\u00e9mies My\u00e9lo\u00efdes Chroniques. 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