{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:54:30Z","timestamp":1783814070432,"version":"3.55.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Field of Zhenjiang \u201cJin Shan Ying Cai\u201d Project"},{"name":"Medical Education Collaborative Innovation Fund of Jiangsu University","award":["JDY2022011"],"award-info":[{"award-number":["JDY2022011"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81900163"],"award-info":[{"award-number":["81900163"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81970118"],"award-info":[{"award-number":["81970118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81900166"],"award-info":[{"award-number":["81900166"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zhenjiang Clinical Research Center of Hematology","award":["SS2018009"],"award-info":[{"award-number":["SS2018009"]}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20221287"],"award-info":[{"award-number":["BK20221287"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Project of Jiangsu Commission of Health","award":["M2022123"],"award-info":[{"award-number":["M2022123"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Aberrant DNA methylation plays a crucial role in the progression of myeloid neoplasms. Previously, our literature reported that slit guidance ligand 2 (<jats:italic>SLIT2<\/jats:italic>) promoter methylation was associated with disease progression and indicated a poor prognosis in patients with myelodysplastic syndrome. Herein, we further investigated the clinical implications and role of <jats:italic>SLIT2<\/jats:italic> promoter methylation in patients with chronic myeloid leukemia (CML).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The level of <jats:italic>SLIT2<\/jats:italic> promoter methylation was determined in 104 CML patients, and its clinical significance was analyzed. Moreover, demethylation studies were performed in K562 cells to determine the epigenetic mechanism by which <jats:italic>SLIT2<\/jats:italic> promoter methylation is regulated in CML.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The level of <jats:italic>SLIT2<\/jats:italic> promoter methylation was similar between CML patients and controls. However, deeper analysis revealed that the <jats:italic>SLIT2<\/jats:italic> promoter methylation level in the accelerated phase (AP) and blast crisis (BC) was markedly higher than that in the chronic phase (CP) and controls. Additionally, a marked difference was identified between the <jats:italic>SLIT2<\/jats:italic> promoter hypermethylated and non-hypermethylated groups among CML patients grouped by clinical stage. The frequency of <jats:italic>SLIT2<\/jats:italic> hypermethylation was markedly increased with the progression of clinical stage, that is, it was the lowest in CP samples (12\/80, 15%), higher in AP samples (4\/8, 50%) and the highest in BC samples (11\/16, 69%). Importantly, the level\/density of <jats:italic>SLIT2<\/jats:italic> promoter methylation was significantly higher in the advanced stage than in the early stage among the 6 tested paired CML patients. Epigenetically, the expression of the <jats:italic>SLIT2<\/jats:italic>-embedded non-coding genes <jats:italic>SLIT2-IT1<\/jats:italic> and <jats:italic>miR-218<\/jats:italic> expression was decreased in patients with CML. <jats:italic>SLIT2<\/jats:italic> promoter hypermethylated cases had a markedly lower <jats:italic>SLIT2-IT1<\/jats:italic> expression level than <jats:italic>SLIT2<\/jats:italic> promoter non-hypermethylated cases. Moreover, <jats:italic>SLIT2-IT1<\/jats:italic> and <jats:italic>miR-218<\/jats:italic> expression was remarkably upregulated in a dose-dependent manner after demethylation treatment of K562 cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Hypermethylation of the <jats:italic>SLIT2<\/jats:italic> promoter is correlated with disease progression in CML. Furthermore, <jats:italic>SLIT2<\/jats:italic> promoter methylation may function by regulating the expression of the <jats:italic>SLIT2<\/jats:italic>-embedded non-coding genes <jats:italic>SLIT2-IT1<\/jats:italic> and <jats:italic>miR-218<\/jats:italic> during CML progression.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40001-022-00899-2","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T05:02:40Z","timestamp":1669006960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SLIT2 promoter hypermethylation predicts disease progression in chronic myeloid leukemia"],"prefix":"10.1186","volume":"27","author":[{"given":"De-long","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-qiang","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-jun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-chun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-dong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"issue":"10314","key":"899_CR1","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1016\/S0140-6736(21)01204-6","volume":"398","author":"J Cortes","year":"2021","unstructured":"Cortes J, Pavlovsky C, Sau\u00dfele S. 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Written informed consents were obtained from all enrolled individuals prior to their participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"259"}}