{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:12:13Z","timestamp":1760148733139,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society Research Scholar Grant","doi-asserted-by":"publisher","award":["RSG-17-044-01-LIB","R01 HG006827"],"award-info":[{"award-number":["RSG-17-044-01-LIB","R01 HG006827"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Human Genome Research Institute (NHGRI)","award":["RSG-17-044-01-LIB","R01 HG006827"],"award-info":[{"award-number":["RSG-17-044-01-LIB","R01 HG006827"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Epigenetic abnormality is a hallmark of acute myeloid leukemia (AML), and aberrant 5-hydroxymethylcytosine (5hmC) levels are commonly observed in AML patients. As epigenetic subgroups of AML correlate with different clinical outcomes, we investigated whether plasma cell-free DNA (cfDNA) 5hmC could categorize AML patients into subtypes. We profiled the genome-wide landscape of 5hmC in plasma cfDNA from 54 AML patients. Using an unbiased clustering approach, we found that 5hmC levels in genomic regions with a histone mark H3K4me3 classified AML samples into three distinct clusters that were significantly associated with leukemia burden and survival. Cluster 3 showed the highest leukemia burden, the shortest overall survival of patients, and the lowest 5hmC levels in the TET2 promoter. 5hmC levels in the TET2 promoter could represent TET2 activity resulting from mutations in DNA demethylation genes and other factors. The novel genes and key signaling pathways associated with aberrant 5hmC patterns could add to our understanding of DNA hydroxymethylation and highlight the potential therapeutic targets in AML. Our results identify a novel 5hmC-based AML classification system and further underscore cfDNA 5hmC as a highly sensitive marker for AML.<\/jats:p>","DOI":"10.3390\/genes14061180","type":"journal-article","created":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T15:29:52Z","timestamp":1685287792000},"page":"1180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Classification of Acute Myeloid Leukemia by Cell-Free DNA 5-Hydroxymethylcytosine"],"prefix":"10.3390","volume":"14","author":[{"given":"Jianming","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpan","family":"Shah","sequence":"additional","affiliation":[{"name":"Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Weill Cornell Medical College, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddhartha","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youli","family":"Zu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA"},{"name":"Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zejuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, Ley, T.J., Miller, C., Ding, L., Raphael, B.J., Mungall, A.J., Robertson, A., Hoadley, K., Triche, T.J., and Laird, P.W. 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