{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:59:35Z","timestamp":1792195175147,"version":"4.4.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["RSG-17-044-01-LIB"],"award-info":[{"award-number":["RSG-17-044-01-LIB"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Epigenet"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). However, MRD cannot be detected in many patients using current methods. We developed a highly sensitive 5-hydroxymethylcytosine (5hmC) signature in cell-free DNA by analyzing 115 AML patients and 86 controls. The 5hmC method detected MRD in 20 of 29 patients with negative MRD by multiparameter flow cytometry and 11 of 14 patients with negative MRD by molecular methods. MRD detection by the 5hmC method was significantly associated with relapse-free survival. This novel method can be used in most AML patients and may significantly impact AML patient management.<\/jats:p>","DOI":"10.1186\/s13148-023-01547-0","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:02:21Z","timestamp":1692871341000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cell-free DNA 5-hydroxymethylcytosine is highly sensitive for MRD assessment in acute myeloid leukemia"],"prefix":"10.1186","volume":"15","author":[{"given":"Jianming","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpan","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha","family":"Ganguly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youli","family":"Zu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"1547_CR1","doi-asserted-by":"crossref","unstructured":"Zjablovskaja P, Florian MC. Acute Myeloid Leukemia: Aging and Epigenetics. Cancers (Basel). 2019;12(1).","DOI":"10.3390\/cancers12010103"},{"key":"1547_CR2","doi-asserted-by":"publisher","first-page":"655","DOI":"10.3389\/fonc.2019.00655","volume":"9","author":"MT Voso","year":"2019","unstructured":"Voso MT, Ottone T, Lavorgna S, Venditti A, Maurillo L, Lo-Coco F, et al. MRD in AML: the role of new techniques. Front Oncol. 2019;9:655.","journal-title":"Front Oncol"},{"issue":"26","key":"1547_CR3","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1182\/blood.2021013626","volume":"138","author":"M Heuser","year":"2021","unstructured":"Heuser M, Freeman SD, Ossenkoppele GJ, Buccisano F, Hourigan CS, Ngai LL, et al. 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2021;138(26):2753\u201367.","journal-title":"Blood"},{"issue":"12","key":"1547_CR4","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1001\/jamaoncol.2020.4600","volume":"6","author":"NJ Short","year":"2020","unstructured":"Short NJ, Zhou S, Fu C, Berry DA, Walter RB, Freeman SD, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol. 2020;6(12):1890\u20139.","journal-title":"JAMA Oncol"},{"issue":"1","key":"1547_CR5","first-page":"12","volume":"39","author":"C Zeng","year":"2019","unstructured":"Zeng C, Stroup EK, Zhang Z, Chiu BC, Zhang W. Towards precision medicine: advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy. Cancer Commun (Lond). 2019;39(1):12.","journal-title":"Cancer Commun (Lond)"},{"key":"1547_CR6","doi-asserted-by":"publisher","first-page":"744990","DOI":"10.3389\/fcell.2021.744990","volume":"9","author":"L Xu","year":"2021","unstructured":"Xu L, Zhou Y, Chen L, Bissessur AS, Chen J, Mao M, et al. Deoxyribonucleic acid 5-hydroxymethylation in cell-free deoxyribonucleic acid, a novel cancer biomarker in the era of precision medicine. Front Cell Dev Biol. 2021;9:744990.","journal-title":"Front Cell Dev Biol"},{"issue":"7","key":"1547_CR7","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1182\/blood-2013-08-518514","volume":"124","author":"LI Kroeze","year":"2014","unstructured":"Kroeze LI, Aslanyan MG, van Rooij A, Koorenhof-Scheele TN, Massop M, Carell T, et al. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. Blood. 2014;124(7):1110\u20138.","journal-title":"Blood"},{"issue":"1","key":"1547_CR8","doi-asserted-by":"publisher","first-page":"12410","DOI":"10.1038\/s41598-022-16685-3","volume":"12","author":"J Shao","year":"2022","unstructured":"Shao J, Wang S, West-Szymanski D, Karpus J, Shah S, Ganguly S, et al. Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia. Sci Rep. 2022;12(1):12410.","journal-title":"Sci Rep"},{"issue":"e136","key":"1547_CR9","first-page":"1","volume":"2","author":"J Shao","year":"2022","unstructured":"Shao J, Bernicker E, He C, Li Z. Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection. Clin Transl Discov. 2022;2(e136):1\u201316.","journal-title":"Clin Transl Discov"},{"issue":"4","key":"1547_CR10","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.molcel.2016.06.028","volume":"63","author":"D Han","year":"2016","unstructured":"Han D, Lu X, Shih AH, Nie J, You Q, Xu MM, et al. A highly sensitive and robust method for genome-wide 5hmC profiling of rare cell populations. Mol Cell. 2016;63(4):711\u20139.","journal-title":"Mol Cell"}],"container-title":["Clinical Epigenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-023-01547-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13148-023-01547-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-023-01547-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T09:02:53Z","timestamp":1700298173000},"score":1,"resource":{"primary":{"URL":"https:\/\/clinicalepigeneticsjournal.biomedcentral.com\/articles\/10.1186\/s13148-023-01547-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,24]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1547"],"URL":"https:\/\/doi.org\/10.1186\/s13148-023-01547-0","relation":{},"ISSN":["1868-7083"],"issn-type":[{"value":"1868-7083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,24]]},"assertion":[{"value":"12 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional review board at Houston Methodist Hospital. The informed consent was waived.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"C.H. is an inventor of the 5hmC-Seal method. All other authors declare no competing interests related to the work described.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"134"}}