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Metabolomic analysis provides a more direct measure of these states, yet most studies remain cross-sectional and lack dynamic insight. In this study, a longitudinal serum metabolomics analysis based on proton nuclear magnetic resonance was conducted in AML patients throughout chemotherapy and in healthy controls. Temporal and response-related metabolic trajectories were analyzed using regression models, and an elastic net logistic regression model was applied to identify metabolite signatures distinguishing remission and relapse. Pathway enrichment analysis was further performed to explore the biological relevance of the metabolic alterations. Longitudinal serum metabolomics of 45 AML patients revealed chemotherapy-induced metabolic reprogramming. Linear and nonlinear temporal trajectories of 16 metabolites distinguished remission status between patient groups (p &amp;lt; 0.05). A subset of these metabolites was consistently selected by machine learning as candidate features that discriminated patients with remission from those with relapse (AUC = 0.909), including alanine, taurine, and valine. Overall, longitudinal serum metabolomics revealed dynamic metabolic patterns in response to chemotherapy in AML, including metabolic signatures that distinguished remission from those of relapse. These findings support the potential of dynamic metabolic profiling for monitoring treatment response and characterizing metabolic alterations associated with disease relapse.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02503","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:21:12Z","timestamp":1788340872000},"page":"26531-26542","source":"Crossref","is-referenced-by-count":0,"title":["Serum Metabolomics Reveals Time-Dynamic Metabolic\nChanges and Candidate Markers Associated with Treatment Response in\nAcute Myeloid Leukemia"],"prefix":"10.1021","volume":"98","author":[{"given":"Rong","family":"Hu","sequence":"first","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]},{"name":"Fujian Province University, Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]},{"name":"Shanghai Fengxian District Center for Disease Control and Prevention (Shanghai Fengxian District Health Inspection Institute) , , ,","place":["Shanghai, China, 201499"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Deng","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]},{"name":"Fujian Province University, Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haishan","family":"Yi","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]},{"name":"Fujian Province University, Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Duan","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine , , ,","place":["Hangzhou, China, 310016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anran","family":"Shi","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingping","family":"Cao","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Duan","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-2750","authenticated-orcid":true,"given":"Jianghua","family":"Feng","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital , , ,","place":["Fuzhou, China, 350001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9255-6502","authenticated-orcid":true,"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]},{"name":"Fujian Province University, Fujian Medical University , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"issue":"1","key":"2026091511091053400_cit1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13045-023-01424-6","article-title":"Recent advances\nin targeted therapies\nin acute myeloid leukemia","volume":"16","author":"Bhansali","year":"2023","journal-title":"J. Hematol. Oncol."},{"issue":"21","key":"2026091511091053400_cit2","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1182\/blood.2025029132","article-title":"Plasma lipid levels\npredict chemotherapy response and survival in acute myeloid leukemia","volume":"146","author":"O\u2019Brien","year":"2025","journal-title":"Blood"},{"issue":"2","key":"2026091511091053400_cit3","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41375-024-02452-y","article-title":"Global\npatterns of leukemia\nby subtype, age, and sex in 185 countries in 2022","volume":"39","author":"Daltveit","year":"2025","journal-title":"Leukemia"},{"issue":"10393","key":"2026091511091053400_cit4","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1016\/S0140-6736(23)00108-3","article-title":"Acute\nmyeloid leukaemia","volume":"401","author":"Di Nardo","year":"2023","journal-title":"The Lancet"},{"issue":"7","key":"2026091511091053400_cit5","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200487R","article-title":"Differentiation\nand prognostic stratification of acute myeloid leukemia\nby serum-based spectroscopy coupling with metabolic fingerprints","volume":"36","author":"Duan","year":"2022","journal-title":"FASEB J."},{"key":"2026091511091053400_cit6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized\nlinear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. 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Hematol."},{"issue":"10","key":"2026091511091053400_cit25","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1038\/s41375-021-01318-x","article-title":"Integrated genomic-metabolic\nclassification of acute myeloid leukemia defines a subgroup with NPM1\nand cohesin\/DNA damage mutations","volume":"35","author":"Simonetti","year":"2021","journal-title":"Leukemia"},{"issue":"2","key":"2026091511091053400_cit26","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3324\/haematol.2022.280800","article-title":"Leukemic stem cells and therapy resistance in acute\nmyeloid leukemia","volume":"108","author":"Stelmach","year":"2023","journal-title":"Haematologica"},{"issue":"1","key":"2026091511091053400_cit27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1182\/bloodadvances.2021004962","article-title":"Transcriptomic analysis\nreveals proinflammatory signatures associated with acute myeloid leukemia\nprogression","volume":"6","author":"Stratmann","year":"2022","journal-title":"Blood Adv."},{"issue":"7","key":"2026091511091053400_cit28","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1182\/blood-2002-04-1199","article-title":"The World\nHealth Organization (WHO)\nclassification of the myeloid neoplasms","volume":"100","author":"Vardiman","year":"2002","journal-title":"Blood"},{"issue":"6","key":"2026091511091053400_cit29","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/s41375-021-01230-4","article-title":"Measurable residual\ndisease as a biomarker in acute myeloid leukemia: theoretical and\npractical considerations","volume":"35","author":"Walter","year":"2021","journal-title":"Leukemia"},{"issue":"10","key":"2026091511091053400_cit30","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.1021\/pr400403p","article-title":"Rapid diagnosis and\nprognosis of de novo acute myeloid leukemia by serum metabonomic analysis","volume":"12","author":"Wang","year":"2013","journal-title":"J. Proteome Res."},{"issue":"7","key":"2026091511091053400_cit31","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1158\/1538-7445.AM2023-3155","article-title":"Gene expression profiles\nreveal distinct regulatory activities of transcription factors GATA1\nand TAL1 upon AML relapse","volume":"83","author":"Wang","year":"2023","journal-title":"Cancer Res."},{"key":"2026091511091053400_cit32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v077.i01","article-title":"ranger: A fast implementation\nof random forests for\nhigh dimensional data in C++ and R","volume":"77","author":"Wright","year":"2017","journal-title":"J. Stat.\nSoftware"},{"issue":"7","key":"2026091511091053400_cit33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41568-020-0260-3","article-title":"Dysregulated haematopoietic\nstem cell behaviour in myeloid leukaemogenesis","volume":"20","author":"Yamashita","year":"2020","journal-title":"Nat. Rev. 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Anal."},{"issue":"12","key":"2026091511091053400_cit36","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41408-021-00591-4","article-title":"Dynamic\nassessment of measurable residual disease in favorable-risk\nacute myeloid leukemia in first remission, treatment, and outcomes","volume":"11","author":"Yu","year":"2021","journal-title":"Blood Cancer J."},{"issue":"1","key":"2026091511091053400_cit37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12943-022-01635-4","article-title":"Longitudinal single-cell\ntranscriptomics reveals distinct patterns of recurrence in acute myeloid\nleukemia","volume":"21","author":"Zhai","year":"2022","journal-title":"Mol. Cancer"},{"issue":"1","key":"2026091511091053400_cit38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12944-022-01687-x","article-title":"A novel fatty acid metabolism-related\nsignature identifies features of the tumor microenvironment and predicts\nclinical outcome in acute myeloid leukemia","volume":"21","author":"Zhang","year":"2022","journal-title":"Lipids Health Dis."},{"issue":"24","key":"2026091511091053400_cit39","doi-asserted-by":"publisher","first-page":"7525","DOI":"10.1182\/bloodadvances.2023010460","article-title":"GPRC5C drives branched-chain\namino acid metabolism in leukemogenesis","volume":"7","author":"Zhang","year":"2023","journal-title":"Blood\nAdv."},{"issue":"1","key":"2026091511091053400_cit40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40364-024-00600-1","article-title":"Application of omics\nin the diagnosis, prognosis, and treatment of acute myeloid leukemia","volume":"12","author":"Zhang","year":"2024","journal-title":"Biomark. Res."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c02503","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26531\/67673039\/acs.analchem.6c02503.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26531\/67673039\/acs.analchem.6c02503.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:20:58Z","timestamp":1789485658000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/36\/26531\/5356327\/Serum-Metabolomics-Reveals-Time-Dynamic-Metabolic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":40,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,8,28]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c02503","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}