{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T01:50:56Z","timestamp":1772070656033,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Anticancer chemotherapy is an underappreciated contributor to cancer cachexia, an often\u2010irreversible body\u2010wasting condition that causes 20%\u201330% of cancer\u2010related deaths. An obstacle to predicting, monitoring and understanding the mechanisms underlying chemotherapy cachexia is that each cancer (and subtype) is assigned different chemotherapeutic compounds, typically in multiagent regimens. Here, we investigate the chemotherapy induction regimen (CIR) used in the haematological cancer, acute myeloid leukaemia (AML). We hypothesised that the AML CIR would induce cachexia, including loss of lean tissue mass and skeletal muscle atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an unbiased proteomics approach, we interrogated the underlying molecular mechanisms. Three\u2010month\u2010old male Balb\/c mice were treated with the AML CIR via intraperitoneal injections of daunorubicin (1.7\u2009mg\/kg) on Days 1\u20133 and cytarabine (33.2\u2009mg\/kg) administered on Days 1\u20137 or vehicle. Mice were assessed 24\u2009h after the last treatment, on Day 8, or allowed to recover for 2\u2009weeks and assessed on Day 22. A third cohort was given access to running wheels in cages. We assessed body composition and whole\u2010body metabolism and assessed the muscle proteome using quantitative tandem mass tag labelling LC\u2013MS\/MS analysis. Data are available via ProteomeXchange with identifier PXD063910.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The AML CIR\u2010induced acute cachexia involved a ~10% loss of body mass, ~10% loss of lean mass and ~20% reduction in skeletal muscle fibre size. Whole\u2010body metabolism and ambulatory activity declined. This cachexic phenotype did not recover over the 2\u2010week post\u2010CIR period (lean mass loss post\u2010CIR: 1\u2009week ~7% vs. 2\u2009weeks ~9%). In voluntarily active CIR\u2010treated mice, body wasting was exacerbated due to unchecked loss of fat mass (CIR sedentary: ~31% vs. CIR active: ~51%). Muscle proteome studies revealed upregulation of haptoglobin (Hp) and glutamine synthetase (Glul), which were positively correlated with body and lean mass loss. Hp was sensitive to the conditional induction, recovery and exacerbation of AML CIR\u2010mediated cachexia, suggestive of biomarker potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The AML CIR induces an acute reduction of body, lean and fat mass underpinned by skeletal muscle atrophy, hypermetabolism and catabolism. Our data uncovered a conditionally sensitive muscle biomarker in Hp, which may be useful as a prognostic tool across other scenarios of chemotherapy\u2010induced myopathy and cachexia or as a target for therapeutic discovery in follow\u2010up studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13849","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T08:20:52Z","timestamp":1749111652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Haptoglobin and Glutamine Synthetase May Biomark Cachexia Induced by Antiacute Myeloid Leukaemia Chemotherapy"],"prefix":"10.1002","volume":"16","author":[{"given":"Dean\u00a0G.","family":"Campelj","sequence":"first","affiliation":[{"name":"Institute for Health and Sport, Victoria University  Melbourne Victoria Australia"},{"name":"Biology of Ageing Laboratory Centre for Healthy Ageing, Centenary Institute  Camperdown New South Wales Australia"},{"name":"Faculty of Medicine and Health, Charles Perkins Centre University of Sydney  Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara\u00a0A.","family":"Timpani","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University  Melbourne Victoria Australia"},{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"},{"name":"Department of Medicine\u2014Western Health Melbourne Medical School, The University of Melbourne  St Albans Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guinevere","family":"Spiesberger","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University  Melbourne Victoria Australia"},{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke\u00a0E.","family":"Formosa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash Biomedicine Discovery Institute, Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel\u00a0R.","family":"Steele","sequence":"additional","affiliation":[{"name":"Monash Proteomics and Metabolomics Platform, Department of Biochemistry and Molecular Biology Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Monash Proteomics and Metabolomics Platform, Department of Biochemistry and Molecular Biology Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf\u00a0B.","family":"Schittenhelm","sequence":"additional","affiliation":[{"name":"Monash Proteomics and Metabolomics Platform, Department of Biochemistry and Molecular Biology Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewis","family":"Leow","sequence":"additional","affiliation":[{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"},{"name":"Department of Medicine\u2014Western Health Melbourne Medical School, The University of Melbourne  St Albans Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig\u00a0A.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research, Department of Anatomy and Physiology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-0036","authenticated-orcid":false,"given":"Emma","family":"Rybalka","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University  Melbourne Victoria Australia"},{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"},{"name":"Department of Medicine\u2014Western Health Melbourne Medical School, The University of Melbourne  St Albans Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13143615"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12880"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31041-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djy233"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/aac2.12027"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13400"},{"issue":"4","key":"e_1_2_9_9_1","first-page":"9","article-title":"Toxicology of Daunorubicin in Animals and Man","volume":"65","author":"Maral R. J.","year":"1981","journal-title":"Cancer Treatment Reports"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V32.4.507.507"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123810"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400329R"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00860"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1011"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","unstructured":"E. H.Rashan A. K.Bartlett D. B.Khana et\u00a0al. ACAD10 and ACAD11 Enable Mammalian 4\u2010Hydroxy Acid Lipid Catabolism. bioRxiv.2024 https:\/\/doi.org\/10.1101\/2024.01.09.574893.","DOI":"10.1101\/2024.01.09.574893"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(86)90002-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3045-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102812"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.790451"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.10.008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100157"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12188"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00472"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34855-X"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2023.100387"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsufs.2019.00115"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00537.2023"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00415"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150606"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61059-2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113221"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2022.01.003"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP281071"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100745"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72931"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041701"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00178.2023"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.2952"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14102512"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-018-4396-6"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.5717\/jenb.2015.15092812"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13849","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:24:06Z","timestamp":1750847046000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jcsm.13849"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13849","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13849"}}