{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:07:05Z","timestamp":1791338825960,"version":"4.3.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA293366"],"award-info":[{"award-number":["R01CA293366"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008615","name":"UNC | UNC-Chapel Hill | Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Effective treatment of pediatric acute leukemia is dependent on accurate genomic classification, typically derived from a combination of multiple time-consuming and costly techniques such as flow cytometry, fluorescence in situ hybridization (FISH), karyotype analysis, targeted PCR, and microarrays [1\u20133]. We investigated the feasibility of a comprehensive single-assay classification approach using long-read sequencing, with real-time genome target enrichment, to classify chromosomal abnormalities and structural variants characteristic of acute leukemia. We performed whole genome sequencing on DNA from diagnostic peripheral blood or bone marrow for 57 pediatric acute leukemia cases with diverse genomic subtypes. We demonstrated the characterization of known, clinically relevant karyotype abnormalities and structural variants concordant with standard-of-care clinical testing. Subtype-defining genomic alterations were identified in all cases following a maximum of 48\u2009h of sequencing. In 18 cases, we performed real-time analysis\u2014 concurrent with sequencing\u2014and identified the driving alteration in as little as 15\u2009min (for karyotype) or up to 6\u2009h (for complex structural variants). Whole genome nanopore sequencing with adaptive sampling has the potential to provide genomic classification of acute leukemia specimens with reduced cost and turnaround time compared to the current standard of care.<\/jats:p>","DOI":"10.1038\/s41375-025-02565-y","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T04:26:26Z","timestamp":1742790386000},"page":"1069-1077","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Real-time genomic characterization of pediatric acute leukemia using adaptive sampling"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-379X","authenticated-orcid":false,"given":"Julie","family":"Geyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kofi B.","family":"Opoku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Ramkissoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-1850","authenticated-orcid":false,"given":"Charles","family":"Mullighan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5282-7833","authenticated-orcid":false,"given":"Nickhill","family":"Bhakta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0484-1574","authenticated-orcid":false,"given":"Thomas B.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-9418","authenticated-orcid":false,"given":"Jeremy R.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"2565_CR1","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","volume":"127","author":"DA Arber","year":"2016","unstructured":"Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391\u2013405.","journal-title":"Blood"},{"key":"2565_CR2","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1200\/JCO.2016.70.7836","volume":"35","author":"I Iacobucci","year":"2017","unstructured":"Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017;35:975\u201383.","journal-title":"J Clin Oncol"},{"key":"2565_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/ijlh.13135","volume":"42","author":"D Narayanan","year":"2020","unstructured":"Narayanan D, Weinberg OK. How I investigate acute myeloid leukemia. 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The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations. Patient specimens were obtained from the University of North Carolina at Chapel Hill (UNC) and St. Jude Children\u2019s Research Hospital (SJCRH) \u201cTBANK\u201d Biorepository with approval by the University of North Carolina at Chapel Hill\u2019s Biomedical Institutional Review Board approvals 17-2609 (Pediatric tumor biobank) and 19-0413 (Novel sequencing-based diagnostics). Informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}