{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:23Z","timestamp":1792789043764,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chiang Mai University","award":["FF084\/2567"],"award-info":[{"award-number":["FF084\/2567"]}],"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"crossref"}]},{"award":["FF084\/2567"],"award-info":[{"award-number":["FF084\/2567"]}],"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Relapse remains the leading cause of mortality in pediatric acute lymphoblastic leukemia (ALL), underscoring the need for novel biomarkers and therapies. The objective of this study is to identify distinct metabolomes associated with relapsed ALL, using bone marrow aspirated at the relapse episode itself, a specimen that is rarely banked and whose metabolome has not previously been reported. Method: This study utilized untargeted liquid chromatography\u2013mass spectrometry (LC-MS) metabolomics on bone marrow aspirates from 21 children with B-lineage ALL. Aliquots from the 12 non-relapsed patients were collected at initial diagnosis and those from the 9 relapsed patients at relapse, so group and disease phase are collinear by design. Results: The resulting metabolic profile clearly distinguished bone marrow sampled at relapse from bone marrow sampled at initial diagnosis. Partial least-squares discriminant analysis separated the two groups, completely in positive ion mode and with 18 of 21 samples correctly classified in negative ion mode (1000-permutation test, p = 0.001 in both modes), and 31 of 92 metabolites in positive ion mode and 3 of 44 in negative ion mode differed after Benjamini\u2013Hochberg correction (q &lt; 0.05), of which 26 and 3 respectively also exceeded the fold-change threshold of |log2FC| &gt; 1. The relapse-associated differences involved carnitine, amino acid and lipid metabolites. O-acetylcarnitine was elevated, which is compatible with increased fatty acid oxidation; dipeptides were higher but not significantly (q = 0.075); L-allo-threonine was elevated, which is compatible with increased flux through the serine\u2013glycine one-carbon pathway; adenosine monophosphate (AMP) was decreased, although the abundance of AMP alone does not provide the AMP: adenosine triphosphate (ATP) ratio and cannot establish the activity of AMP-activated protein kinase (AMPK) or of mammalian target of rapamycin complex 1 (mTORC1); and individual lipid species differed in both directions. These are hypotheses generated by the observed differences in metabolite abundance and are not mechanisms demonstrated by this study. Conclusions: This exploratory comparison describes the metabolite composition of bone marrow at relapse and identifies fatty acid oxidation, the serine\u2013glycine one-carbon pathway and ether-lipid metabolism as priorities for future investigation rather than as established therapeutic dependencies. Because the relapsed specimens were obtained at relapse, the signature describes relapsed disease and is not evidence that relapse can be predicted at diagnosis.<\/jats:p>","DOI":"10.3390\/cancers18183064","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Bone Marrow Metabolic Profiles at Relapse Compared with Initial Diagnosis in Pediatric Acute Lymphoblastic Leukemia\u2014An LC-MS Metabolomics Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-6682","authenticated-orcid":false,"given":"Sivamoke","family":"Dissook","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9163-3682","authenticated-orcid":false,"given":"Romteera","family":"Kittichaiworakul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-9062","authenticated-orcid":false,"given":"Patcharawadee","family":"Thongkumkoon","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-9998","authenticated-orcid":false,"given":"Pitiporn","family":"Noisagul","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kanda","family":"Fanhchaksai","sequence":"additional","affiliation":[{"name":"Thalassemia and Hematology Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Lalita","family":"Sathitsamitphong","sequence":"additional","affiliation":[{"name":"Thalassemia and Hematology Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-1162","authenticated-orcid":false,"given":"Chane","family":"Choed-Amphai","sequence":"additional","affiliation":[{"name":"Thalassemia and Hematology Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-9177","authenticated-orcid":false,"given":"Pimlak","family":"Charoenkwan","sequence":"additional","affiliation":[{"name":"Thalassemia and Hematology Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-5578","authenticated-orcid":false,"given":"Parunya","family":"Chaiyawat","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5210-5398","authenticated-orcid":false,"given":"Apiwat","family":"Sangphukieo","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Rungrote","family":"Natesirinilkul","sequence":"additional","affiliation":[{"name":"Thalassemia and Hematology Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/S0140-6736(12)62187-4","article-title":"Acute lymphoblastic leukaemia","volume":"381","author":"Inaba","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1200\/JCO.2014.59.1636","article-title":"Childhood acute lymphoblastic leukemia: Progress through collaboration","volume":"33","author":"Pui","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e170580","DOI":"10.1001\/jamaoncol.2017.0580","article-title":"Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis","volume":"3","author":"Berry","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1182\/blood-2015-03-580027","article-title":"Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies","volume":"125","author":"Orfao","year":"2015","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vllahu, M., Savarese, M., Cantiello, I., Munno, C., Sarcina, R., Stellato, P., Leone, O., and Alfieri, M. (2025). Application of omics analyses in pediatric B-cell acute lymphoblastic leukemia. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020424"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e39782","DOI":"10.1097\/MD.0000000000039782","article-title":"Metabolomics for hematologic malignancies: Advances and perspective","volume":"103","author":"Li","year":"2024","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Papadopoulou, M.T., Panagopoulou, P., Paramera, E., Pechlivanis, A., Virgiliou, C., Papakonstantinou, E., Palabougiouki, M., Ioannidou, M., Vasileiou, E., and Tragiannidis, A. (2024). Metabolic fingerprint in childhood acute lymphoblastic leukemia. Diagnostics, 14.","DOI":"10.3390\/diagnostics14070682"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ebiom.2019.09.033","article-title":"Metabolomic profiling identifies pathways associated with minimal residual disease in childhood acute lymphoblastic leukaemia","volume":"48","author":"Schraw","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.cca.2014.05.022","article-title":"Biomarker identification and pathway analysis by serum metabolomics of childhood acute lymphoblastic leukemia","volume":"436","author":"Bai","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13052-025-01921-z","article-title":"LC-MS analysis of serum lipidomic and metabolomic signatures in pediatric patients with acute lymphoblastic leukemia","volume":"51","author":"Yan","year":"2025","journal-title":"Ital. J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/MOH.0000000000000853","article-title":"Unraveling lipid metabolism for acute myeloid leukemia therapy","volume":"32","author":"Jones","year":"2025","journal-title":"Curr. Opin. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Raza, Y., Salman, H., and Luberto, C. (2021). Sphingolipids in hematopoiesis: Exploring their role in lineage commitment. Cells, 10.","DOI":"10.3390\/cells10102507"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbacli.2017.03.002","article-title":"The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features","volume":"7","author":"Pabst","year":"2017","journal-title":"BBA Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41420-018-0075-0","article-title":"Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies","volume":"4","author":"Lewis","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrc.2017.96","article-title":"Sphingolipid metabolism in cancer signalling and therapy","volume":"18","author":"Ogretmen","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s10238-024-01440-x","article-title":"Targeting sphingolipid metabolism in chronic lymphocytic leukemia","volume":"24","author":"Le","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrm1103","article-title":"Sphingosine-1-phosphate: An enigmatic signalling lipid","volume":"4","author":"Spiegel","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1182\/blood.2019001034","article-title":"Amino acid metabolism in hematologic malignancies and the era of targeted therapy","volume":"134","author":"Tabe","year":"2019","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ccell.2019.12.011","article-title":"Emerging roles for branched-chain amino acid metabolism in cancer","volume":"37","author":"Sivanand","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ozawa, H., Hirayama, A., Shoji, F., Maruyama, M., Suzuki, K., Yamanaka-Okumura, H., Tatano, H., Morine, Y., Soga, T., and Shimada, M. (2020). Comprehensive dipeptide analysis revealed cancer-specific profile in the liver of patients with hepatocellular carcinoma and hepatitis. Metabolites, 10.","DOI":"10.3390\/metabo10110442"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: Metabolism, functions, and nutrition","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1097\/MPH.0b013e3181ca9eb9","article-title":"Serum carnitine levels in childhood leukemia","volume":"32","author":"Rogalidou","year":"2010","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrc3483","article-title":"Cancer metabolism: Fatty acid oxidation in the limelight","volume":"13","author":"Carracedo","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8128","DOI":"10.1021\/acsomega.2c00083","article-title":"Diagnostic value of 1H NMR-based metabolomics in acute lymphoblastic leukemia, acute myeloid leukemia, and breast cancer","volume":"7","author":"Morad","year":"2022","journal-title":"ACS Omega"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s13539-011-0017-7","article-title":"L-carnitine and cancer cachexia: Clinical and experimental aspects","volume":"2","author":"Laviano","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Andresen, C., Boch, T., Gegner, H.M., Mechtel, N., Narr, A., Birgin, E., Rasbach, E., Rahbari, N., Trumpp, A., and Poschet, G. (2022). Comparison of extraction methods for intracellular metabolomics of human tissues. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.932261"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41419-018-0313-7","article-title":"The carnitine system and cancer metabolic plasticity","volume":"9","author":"Melone","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.devcel.2021.04.013","article-title":"Lipid metabolism in cancer: New perspectives and emerging mechanisms","volume":"56","author":"Broadfield","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41467-026-68547-5","article-title":"Ether lipids influence cancer cell fate by modulating iron uptake","volume":"17","author":"Mansell","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/mc.20770","article-title":"Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade","volume":"51","author":"Kuc","year":"2012","journal-title":"Mol. Carcinog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41392-025-02238-3","article-title":"Cancer cell cooperation: Tumor cells team up to scavenge nutrients to ensure proliferation despite starvation","volume":"10","author":"Sebens","year":"2025","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41586-025-08588-w","article-title":"Cooperative nutrient scavenging is an evolutionary advantage in cancer","volume":"640","author":"Guzelsoy","year":"2025","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wu, Q., Li, J., Zhu, J., Sun, X., He, D., Li, J., Cheng, Z., Zhang, X., Xu, Y., and Chen, Q. (2022). Gamma-glutamyl-leucine levels are causally associated with elevated cardio-metabolic risks. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.936220"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e201907022","DOI":"10.1083\/jcb.201907022","article-title":"The complexity of the serine glycine one-carbon pathway in cancer","volume":"219","author":"Moscat","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3892\/ijo.2020.5158","article-title":"Serine, glycine and onecarbon metabolism in cancer (review)","volume":"58","author":"Pan","year":"2021","journal-title":"Int. J. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wells, G., Kennedy, P.T., and Dahal, L.N. (2021). Investigating the role of indoleamine 2,3-dioxygenase in acute myeloid leukemia: A systematic review. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.651687"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrc2676","article-title":"The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression","volume":"9","author":"Shackelford","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"811","DOI":"10.18632\/oncotarget.579","article-title":"Harnessing the PI3K\/Akt\/mTOR pathway in T-cell acute lymphoblastic leukemia: Eliminating activity by targeting at different levels","volume":"3","author":"Bressanin","year":"2012","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Evangelisti, C., Chiarini, F., McCubrey, J.A., and Martelli, A.M. (2018). Therapeutic targeting of mTOR in T-cell acute lymphoblastic leukemia: An update. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071878"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"Panwar","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.stem.2020.07.021","article-title":"Nicotinamide metabolism mediates resistance to venetoclax in relapsed acute myeloid leukemia stem cells","volume":"27","author":"Jones","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12672-025-01893-w","article-title":"Anti-tumor potential of Harmine and its derivatives: Recent trends and advancements","volume":"16","author":"Joshi","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fu, D., Wu, D., Cheng, W., Gao, J., Zhang, Z., Ge, J., Zhou, W., and Xu, Z. (2020). Costunolide induces autophagy and apoptosis by activating ROS\/MAPK signaling pathways in renal cell carcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.582273"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Qi, Y., Duan, G., Wei, D., Zhao, C., and Ma, Y. (2022). The bile acid membrane receptor TGR5 in cancer: Friend or foe?. Molecules, 27.","DOI":"10.3390\/molecules27165292"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1172\/JCI38942","article-title":"Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction","volume":"120","author":"Samudio","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ji, M., Ji, M., Zhong, Y., and Shao, L. (2025). Gut microbiota in acute myeloid leukemia: From biomarkers to interventions. Metabolites, 15.","DOI":"10.3390\/metabo15090568"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:22:50Z","timestamp":1790137370000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/3064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":48,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18183064"],"URL":"https:\/\/doi.org\/10.3390\/cancers18183064","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}