{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:15:10Z","timestamp":1788531310360,"version":"build-2803163510"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>This review critically evaluated the relationship between obesity and survival outcomes in Acute Lymphoblastic Leukemia (ALL), highlighting key evidence gaps and exploring the biological mechanisms that may contribute to this association. In patients with ALL, obesity is consistently associated with a higher incidence of severe treatment-related toxicities, increased frequency of therapy delays, and reduced event-free survival. This connection is most pronounced in pediatric and adolescent ALL populations, whereas evidence supporting a similar effect in adults remains limited. Proposed biological mechanisms underlying these adverse outcomes include increased bone marrow adiposity, chronic low-grade inflammation, dysregulated insulin signaling and obesity-associated alterations in the gut microbiome. The current body of evidence identifies obesity as a clinically significant risk factor that defines a vulnerable subgroup of ALL patients, supporting the need for enhanced toxicity surveillance, individualized treatment strategies, and optimized supportive care interventions. Elucidation of the biological pathways linking obesity to adverse ALL outcomes may also inform the development of novel therapeutic approaches aimed at mitigating obesity-driven morbidity and mortality in this high-risk population.<\/jats:p>","DOI":"10.3389\/fonc.2026.1918955","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:23:21Z","timestamp":1788528201000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical evidence and biological mechanisms linking obesity to adverse outcomes in pediatric and adolescent acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Cate","family":"Cheney","sequence":"first","affiliation":[{"name":"Targeted Leuakemia Research Group, South Australian Health and Medical Research Institute","place":["Adelaide, SA, Australia"]},{"name":"College of Health, Adelaide University","place":["Adelaide, SA, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Page","sequence":"additional","affiliation":[{"name":"Targeted Leuakemia Research Group, South Australian Health and Medical Research Institute","place":["Adelaide, SA, Australia"]},{"name":"College of Health, Adelaide University","place":["Adelaide, SA, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yeung","sequence":"additional","affiliation":[{"name":"Targeted Leuakemia Research Group, South Australian Health and Medical Research Institute","place":["Adelaide, SA, Australia"]},{"name":"Department of Haematology, The Royal Adelaide Hospital","place":["Adelaide, SA, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"White","sequence":"additional","affiliation":[{"name":"Targeted Leuakemia Research Group, South Australian Health and Medical Research Institute","place":["Adelaide, SA, Australia"]},{"name":"College of Health, Adelaide University","place":["Adelaide, SA, Australia"]},{"name":"Australian and New Zealand Children\u2019s Oncology Group (ANZCHOG)","place":["Clayton, VIC, Australia"]},{"name":"Australian Genomics Health Alliance (AGHA), The Murdoch Children\u2019s Research Institute","place":["Parkville, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1542649","article-title":"Analysis of global trends in acute lymphoblastic leukemia in children aged 0-5 years from 1990 to 2021","volume":"13","author":"Ding","year":"2025","journal-title":"Front Pediatr"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0330479","article-title":"Analysis of global, regional, and national burden and attributable risk factors of acute lymphoblastic leukemia and acute myeloid leukemia from 1990 to 2021","volume":"20","author":"Ni","year":"2025","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02166-1","article-title":"Enhanced risk stratification for children and young adults with B-cell acute lymphoblastic leukemia: A Children's Oncology Group report","volume":"38","author":"DelRocco","year":"2024","journal-title":"Leukemia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"B5","article-title":"Levels and trends in child malnutritions: Key findings of the 2025 edition of the joint child malnutririon estimates","volume-title":"World Health Institution","year":"2025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.285788","article-title":"Changes in asparaginase exposure and toxicity profiles in obese pediatric acute lymphoblastic leukemia patients","volume":"110","author":"Panetta","year":"2025","journal-title":"Haematologica"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15268-3","article-title":"Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies","volume":"363","year":"2004","journal-title":"Lancet"},{"key":"B8","article-title":"Identifying and assessing overweight, obesity and central adiposity","year":"2026"},{"key":"B9","article-title":"Body mass index (BMI) - related indicators","volume-title":"The Global Health Observatory","year":"2025"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)32129-3","article-title":"Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults","volume":"390","author":"Abarca-G\u00f3mez","year":"2017","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.70095","article-title":"Contributions of clinical obesity and preclinical obesity to the all-cause mortality risk: Findings from the UK Biobank cohort","volume":"41","author":"Xu","year":"2025","journal-title":"Diabetes Metab Res Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.3520","article-title":"Association of obesity with survival outcomes in patients with cancer: A systematic review and meta-analysis","volume":"4","author":"Petrelli","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci127201","article-title":"Adipocyte and lipid metabolism in cancer drug resistance","volume":"129","author":"Cao","year":"2019","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-023-04601-z","article-title":"Are novel oral oncolytics underdosed in obese patients","volume":"93","author":"Lin","year":"2024","journal-title":"Cancer Chemother Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115281","article-title":"Pharmacokinetics of obese adults: Not only an increase in weight","volume":"166","author":"Gouju","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.01.019","article-title":"Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee","volume":"20","author":"Bubalo","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m116.768408","article-title":"Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice","volume":"292","author":"Nikonorova","year":"2017","journal-title":"J Biol Chem"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.247031","article-title":"Pediatric acute lymphoblastic leukemia","volume":"105","author":"Inaba","year":"2020","journal-title":"Haematologica"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/mph.0000000000001604","article-title":"Obesity as a potential risk factor for vincristine-induced peripheral neuropathy","volume":"42","author":"Sajdyk","year":"2020","journal-title":"J Pediatr Hematol Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/cncr.34529","article-title":"Body mass index during maintenance therapy and relapse risk in children with acute lymphoblastic leukemia: A Children's Oncology Group report","volume":"129","author":"Wadhwa","year":"2023","journal-title":"Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17936","article-title":"Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia","volume":"196","author":"Egnell","year":"2022","journal-title":"Br J Haematol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27515","article-title":"Obesity in pediatric patients with acute lymphoblastic leukemia increases the risk of adverse events during pre-maintenance chemotherapy","volume":"66","author":"Meenan","year":"2019","journal-title":"Pediatr Blood Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.thromres.2018.02.150","article-title":"Obesity and risk for venous thromboembolism from contemporary therapy for pediatric acute lymphoblastic leukemia","volume":"165","author":"Prasca","year":"2018","journal-title":"Thromb Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2023.107017","article-title":"Obesogenic microbial signatures and the development of obesity in childhood acute lymphoblastic leukemia","volume":"126","author":"Park","year":"2023","journal-title":"Leuk Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-595389","article-title":"Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia","volume":"124","author":"Orgel","year":"2014","journal-title":"Blood"},{"key":"B26","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1182\/blood.2021011106","article-title":"Increased prevalence of CRLF2 rearrangements in obesity-associated acute lymphoblastic leukemia","volume":"138","author":"Orgel","year":"2021","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.31557\/apjcp.2024.25.7.2361","article-title":"Nutritional status and body composition at diagnosis, of South Indian children with acute lymphoblastic leukaemia (ALL)","volume":"25","author":"Puttaswamy","year":"2024","journal-title":"Asian Pacific J Cancer Prev APJCP"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3334","article-title":"Body mass index associated with childhood and adolescent high-risk B-cell acute lymphoblastic leukemia risk: A Children's Oncology Group report","volume":"9","author":"Ghosh","year":"2020","journal-title":"Cancer Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.9952","article-title":"Overweight or obesity and outcomes in children with acute lymphoblastic leukemia","volume":"8","author":"Ladas","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B30","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1186\/s12885-019-5878-8","article-title":"Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study","volume":"19","author":"N\u00fa\u00f1ez-Enr\u00edquez","year":"2019","journal-title":"BMC Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1182\/blood-2025-1542","article-title":"Obesity is associated with poor prognosis in ph-like acute lymphoblastic leukemia","volume":"146","author":"Zarrabi","year":"2025","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3760","DOI":"10.1182\/blood-2023-178401","article-title":"Trends of obesity over time and its prognostic significance in children and adolescents with newly-diagnosed acute lymphoblastic leukemia in Canada: A population-based study","volume":"142","author":"Sassine","year":"2023","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"155896","DOI":"10.1016\/j.cyto.2022.155896","article-title":"High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia","volume":"155","author":"Juarez-Velazquez","year":"2022","journal-title":"Cytokine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1158\/1538-7445.am2019-3118","article-title":"Abstract 3118: Obesity as a risk factor for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology Group","volume":"79","author":"Ghosh","year":"2019","journal-title":"Cancer Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.160507","article-title":"Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia","volume":"102","author":"Signe Sloth","year":"2017","journal-title":"Haematologica"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1799","article-title":"Effect of body fat on population pharmacokinetics of high-dose methotrexate in pediatric patients with acute lymphoblastic leukemia","volume":"61","author":"Orgel","year":"2021","journal-title":"J Clin Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.32108","article-title":"Visceral fat and body fat as risk factors for methotrexate toxicity in pediatric acute lymphoblastic leukemia and lymphoblastic lymphoma","volume":"73","author":"Garcia-Guzman","year":"2026","journal-title":"Pediatr Blood Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2165\/11318100-000000000-00000","article-title":"Effect of obesity on the pharmacokinetics of drugs in humans","volume":"49","author":"Hanley","year":"2010","journal-title":"Clin Pharmacokinet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1440287","article-title":"Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters","volume":"14","author":"Smit","year":"2018","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00404-026-08317-2","article-title":"Impact of chemotherapy dose capping on treatment intensity and survival in early breast cancer patients with high body surface area","volume":"313","author":"Englisch","year":"2026","journal-title":"Arch Gynecol Obstet"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04159.x","article-title":"Therapeutic drug monitoring to adjust dosing in morbid obesity - a new use for an old methodology","volume":"73","author":"Martin","year":"2012","journal-title":"Br J Clin Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.00471","article-title":"Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update","volume":"39","author":"Griggs","year":"2021","journal-title":"J Clin Oncol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/ftd.0000000000000238","article-title":"Individual 5-fluorouracil dose adjustment via pharmacokinetic monitoring versus conventional body-area-surface method: A meta-analysis","volume":"38","author":"Yang","year":"2016","journal-title":"Ther Drug Monit"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.116.177741","article-title":"In vivo imaging of antileukemic drug asparaginase reveals a rapid macrophage-mediated clearance from the bone marrow","volume":"58","author":"Van Der Meer","year":"2017","journal-title":"J Nucl Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1186\/s12885-021-08443-x","article-title":"Evaluation of body-surface-area adjusted dosing of high-dose methotrexate by population pharmacokinetics in a large cohort of cancer patients","volume":"21","author":"Arshad","year":"2021","journal-title":"BMC Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2025.300277","article-title":"Successful re-exposure to high-dose methotrexate after severely delayed methotrexate elimination and renal toxicity in children with acute lymphoblastic leukemia","volume":"111","author":"Barzilai-Birenboim","year":"2026","journal-title":"Haematologica"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.12.018","article-title":"Delayed cytogenetic and major molecular responses associated to increased BMI at baseline in chronic myeloid leukemia patients treated with imatinib","volume":"333","author":"Breccia","year":"2013","journal-title":"Cancer Lett"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.3738","article-title":"How I treat obesity and obesity related surgery in patients with chronic myeloid leukemia: An outcome of an ELN project","volume":"9","author":"Yassin","year":"2021","journal-title":"Clin Case Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1177\/09636897251349377","article-title":"Prognostic effect of body mass index in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation: A retrospective cohort study","volume":"34","author":"Yu","year":"2025","journal-title":"Cell Transplant"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-204446","article-title":"Effects of obesity on stem cell transplant outcomes in acute myeloid leukemia patients: A systematic review and meta-analysis","author":"Saowapa","year":"2024"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1177\/1078155218772329","article-title":"Outcomes in obese patients undergoing induction therapy for acute leukemia","volume":"25","author":"Dombrowski","year":"2019","journal-title":"J Oncol Pharm Pract"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1080\/0284186x.2023.2258450","article-title":"Impact of body mass index on outcome and treatment-related toxicity in young adults with acute lymphoblastic leukemia","volume":"62","author":"Egnell","year":"2023","journal-title":"Acta Oncol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1007\/s00277-025-06338-6","article-title":"The impact of obesity and its related underlying diseases on cytokine release syndrome and the efficacy of CAR-T therapy in treating B-cell Malignancies","volume":"104","author":"Du","year":"2025","journal-title":"Ann Hematol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023009976","article-title":"Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials","volume":"7","author":"Shimony","year":"2023","journal-title":"Blood Adv"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005576","article-title":"An MRD-stratified pediatric protocol is as deliverable in adolescents and young adults as in children with ALL","volume":"5","author":"Greenwood","year":"2021","journal-title":"Blood Adv"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-163336","article-title":"Obesity associates with inferior outcomes and toxicity in pediatric and young adult patient with relapsed\/refractory B-cell acute lymphoblastic leukemia treated with commercially manufactured tisagenlecleucel","volume":"140","author":"Ross","year":"2022","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-178353","article-title":"Venous thromboembolism in adolescents and young adults with acute lymphoblastic leukemia treated on a pediatric-inspired regimen","volume":"14","author":"Shimony","year":"2024","journal-title":"Blood Cancer J"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70291","article-title":"Blinatumomab in de novo AYA ALL-Results of the Australasian Leukaemia and Lymphoma Group ALL09 \"SUBLIME\" study","volume":"10","author":"Greenwood","year":"2026","journal-title":"Hemasphere"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/mph.0000000000002771","article-title":"Severe methotrexate toxicity following a capizzi cycle in an obese adolescent with acute lymphoblastic leukemia and hepatic steatosis","volume":"46","author":"Fischer","year":"2024","journal-title":"J Pediatr Hematol Oncol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"398","DOI":"10.4997\/jrcpe.2020.409","article-title":"Retrospective studies - utility and caveats","volume":"50","author":"Talari","year":"2020","journal-title":"J R Coll Physicians Edinb"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2008.87","article-title":"BMI-related errors in the measurement of obesity","volume":"32","author":"Rothman","year":"2008","journal-title":"Int J Obes (Lond)"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.21037\/qims.2020.03.02","article-title":"Body composition with dual energy X-ray absorptiometry: from basics to new tools","volume":"10","author":"Messina","year":"2020","journal-title":"Quant Imaging Med Surg"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.23750\/abm.v94i3.13755","article-title":"Value of waist-to-hip ratio as a predictor of metabolic syndrome in adolescents with obesity","volume":"94","author":"Widjaja","year":"2023","journal-title":"Acta BioMed"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41430-023-01310-x","article-title":"The bioelectrical impedance analysis (BIA) international database: aims, scope, and call for data","volume":"77","author":"Silva","year":"2023","journal-title":"Eur J Clin Nutr"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2015.1136741","article-title":"Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy","volume":"59","author":"Orgel","year":"2018","journal-title":"Leuk Lymphoma"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28910","article-title":"A bilingual dietary intervention early in treatment is feasible and prevents weight gain in childhood acute lymphoblastic leukemia","volume":"68","author":"Walters","year":"2021","journal-title":"Pediatr Blood Cancer"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1097\/mph.0000000000000975","article-title":"Early nutrition intervention attenuates weight gain for pediatric acute lymphoblastic leukemia patients in maintenance therapy","volume":"40","author":"Hill","year":"2018","journal-title":"J Pediatr Hematol Oncol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/abm\/kaaf090","article-title":"Adaptation of family-based health promotion to pediatric acute lymphoblastic leukemia treatment: NOURISH-ALL","volume":"59","author":"Bates","year":"2025","journal-title":"Ann Behav Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017004960","article-title":"Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia","volume":"1","author":"Cahu","year":"2017","journal-title":"Blood Adv"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4657","article-title":"Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection","volume":"35","author":"Perez-Figueroa","year":"2016","journal-title":"Oncol Rep"},{"key":"B71","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1186\/s12887-024-05118-x","article-title":"Evaluation of insulin-like growth factor-1 in apparently healthy infants and prepubertal Egyptian children with different nutritional statuses","volume":"24","author":"Fouad","year":"2024","journal-title":"BMC Pediatr"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.172","article-title":"The brain and immune system prompt energy shortage in chronic inflammation and ageing","volume":"13","author":"Straub","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.786129","article-title":"Origin and development of the adipose tissue, a key organ in physiology and disease","volume":"9","author":"Parra-Peralbo","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"3097","DOI":"10.1038\/s41467-020-16878-2","article-title":"Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis","volume":"11","author":"Suchacki","year":"2020","journal-title":"Nat Commun"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-019-00550-w","article-title":"Marrow fat-secreted factors as biomarkers for osteoporosis","volume":"17","author":"Herrmann","year":"2019","journal-title":"Curr Osteoporos Rep"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00694","article-title":"Bone marrow fat and hematopoiesis","volume":"9","author":"Wang","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1652047","article-title":"Chemotherapy-induced senescence, an adaptive mechanism driving resistance and tumor heterogeneity","volume":"18","author":"Guillon","year":"2019","journal-title":"Cell Cycle"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.12.001","article-title":"CD44 promotes chemoresistance in T-ALL by increased drug efflux","volume":"44","author":"Hoofd","year":"2016","journal-title":"Exp Hematol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/s41467-022-28839-y","article-title":"Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia","volume":"13","author":"Lee","year":"2022","journal-title":"Nat Commun"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat Med"},{"key":"B81","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41392-025-02486-3","article-title":"Adipocytes orchestrate obesity-related chronic inflammation through beta2-microglobulin","volume":"10","author":"Li","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00306.2020","article-title":"The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism","volume":"319","author":"Wueest","year":"2020","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01103-8","article-title":"Adipokines: masterminds of metabolic inflammation","volume":"25","author":"Tilg","year":"2025","journal-title":"Nat Rev Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1159\/000054536","article-title":"The long form of the leptin receptor (OB-Rb) is widely expressed in the human brain","volume":"71","author":"Burguera","year":"2000","journal-title":"Neuroendocrinology"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199602013340503","article-title":"Serum immunoreactive-leptin concentrations in normal-weight and obese humans","volume":"334","author":"Considine","year":"1996","journal-title":"N Engl J Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000184","article-title":"Leptin applications in 2015: what have we learned about leptin and obesity","volume":"22","author":"Farr","year":"2015","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1177\/0961203317703497","article-title":"Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency","volume":"26","author":"Wang","year":"2017","journal-title":"Lupus"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2019.103994","article-title":"Leptin induces immunosenescence in human B cells","volume":"348","author":"Frasca","year":"2020","journal-title":"Cell Immunol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1179\/1607845412y.0000000059","article-title":"Impact of serum adiponectin and leptin levels in acute leukemia","volume":"18","author":"Aref","year":"2013","journal-title":"Hematology"},{"key":"B90","article-title":"Serum adiponectin and resistin levels in de novo and relapsed acute lymphoblastic leukemia children patients","volume":"42","author":"El-Baz","year":"2013","journal-title":"Iran J Public Health"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.797836","article-title":"Prognostic observational analysis of BMI, leptin, and adiponectin in children with acute lymphocytic leukemia undergoing remission-induction chemotherapy","volume":"10","author":"Sun","year":"2022","journal-title":"Front Pediatr"},{"key":"B92","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1097\/mph.0b013e3181b8a50c","article-title":"Serial plasma concentrations of adiponectin, leptin, and resistin during therapy in children with acute lymphoblastic leukemia","volume":"32","author":"Moschovi","year":"2010","journal-title":"J Pediatr Hematol Oncol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nm.4252","article-title":"Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation","volume":"23","author":"Lu","year":"2017","journal-title":"Nat Med"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eow014","article-title":"Mouse models of human disease: An evolutionary perspective","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol Med Public Health"},{"key":"B95","article-title":"Insulin resistance","volume-title":"Statpearls","author":"Freeman","year":"2025"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30729","article-title":"Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study","volume":"141","author":"Tsujimoto","year":"2017","journal-title":"Int J Cancer"},{"key":"B97","article-title":"High prevalence of metabolic syndrome and insulin resistance in adolescents receiving chemotherapy for acute lymphoblastic leukemia","volume":"96","author":"Purnamasari","year":"2025","journal-title":"Acta Biomedica"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1097\/mph.0000000000002494","article-title":"Drug induced diabetes mellitus in pediatric acute lymphoblastic leukemia: approach to diagnosis and management","volume":"44","author":"Handattu","year":"2022","journal-title":"J Pediatr Hematol Oncol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.010785","article-title":"Autocrine IGF-1\/IGF-1R signaling is responsible for constitutive PI3K\/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody","volume":"95","author":"Chapuis","year":"2010","journal-title":"Haematologica"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110121","article-title":"High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling","volume":"208","author":"Medyouf","year":"2011","journal-title":"J Exp Med"},{"key":"B101","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s12185-012-1234-3","article-title":"Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia","volume":"97","author":"Yamada","year":"2013","journal-title":"Int J Hematol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ghir.2017.11.001","article-title":"IGF-1R mRNA expression is increased in obese children","volume":"39","author":"Ricco","year":"2018","journal-title":"Growth Hormone IGF Res"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10881","article-title":"GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K\/AKT pathways","volume":"8","author":"Ye","year":"2017","journal-title":"Oncotarget"},{"key":"B104","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.canlet.2019.04.030","article-title":"IGF1R\/IRS1 targeting has cytotoxic activity and inhibits PI3K\/AKT\/mTOR and MAPK signaling in acute lymphoblastic leukemia cells","volume":"456","author":"Rodrigues Alves","year":"2019","journal-title":"Cancer Lett"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2018\/e566s","article-title":"Insulin Substrate Receptor (IRS) proteins in normal and Malignant hematopoiesis","volume":"73","author":"Machado-Neto","year":"2018","journal-title":"Clinics (Sao Paulo)"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.11.15824","article-title":"The insulin receptor substrate (IRS) proteins: at the intersection of metabolism and cancer","volume":"10","author":"Shaw","year":"2011","journal-title":"Cell Cycle"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25845","article-title":"IRS1\/beta-Catenin axis is activated and induces MYC expression in acute lymphoblastic leukemia cells","volume":"118","author":"Fernandes","year":"2017","journal-title":"J Cell Biochem"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1186\/1750-2187-5-15","article-title":"AMPK-induced activation of Akt by AICAR is mediated by IGF-1R dependent and independent mechanisms in acute lymphoblastic leukemia","volume":"5","author":"Leclerc","year":"2010","journal-title":"J Mol Signal"},{"key":"B109","article-title":"Obesity and dyslipidemia","volume-title":"Endotext","author":"Feingold","year":"2000"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-023-00518-z","article-title":"Obesity and dyslipidemia: A review of current evidence","volume":"12","author":"Vekic","year":"2023","journal-title":"Curr Obes Rep"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0231209","article-title":"Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia","volume":"15","author":"Mogensen","year":"2020","journal-title":"PloS One"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103264","article-title":"Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study","volume":"65","author":"Fryk","year":"2021","journal-title":"EBioMedicine"},{"key":"B113","doi-asserted-by":"publisher","first-page":"14883","DOI":"10.1038\/s41598-018-33224-1","article-title":"Alteration of serum free fatty acids are indicators for progression of pre-leukaemia diseases to leukaemia","volume":"8","author":"Khalid","year":"2018","journal-title":"Sci Rep"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.280147","article-title":"Interplay between hypertriglyceridemia and acute promyelocytic leukemia mediated by the cooperation of peroxisome proliferator-activated receptor-alpha with the PML\/RAR alpha fusion protein on super-enhancers","volume":"107","author":"Wu","year":"2022","journal-title":"Haematologica"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1093\/pcmedi\/pbz017","article-title":"The expanded role of fatty acid metabolism in cancer: New aspects and targets","volume":"2","author":"Chen","year":"2019","journal-title":"Precis Clin Med"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.665763","article-title":"Adipocytes provide fatty acids to acute lymphoblastic leukemia cells","volume":"11","author":"Tucci","year":"2021","journal-title":"Front Oncol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i25.3837","article-title":"Gut microbiota in obesity","volume":"27","author":"Liu","year":"2021","journal-title":"World J Gastroenterol"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1002\/path.5134","article-title":"Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes","volume":"246","author":"Genser","year":"2018","journal-title":"J Pathol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1793","article-title":"The integrated \"multiomics\" landscape at peak injury and resolution from alcohol-associated liver disease","volume":"6","author":"Das","year":"2022","journal-title":"Hepatol Commun"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1530\/ey.15.12.8","article-title":"Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection","volume":"359","author":"Thaiss","year":"2018","journal-title":"Science"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9474896","article-title":"High fat diet alters gut microbiota and the expression of Paneth cell-antimicrobial peptides preceding changes of circulating inflammatory cytokines","volume":"2017","author":"Guo","year":"2017","journal-title":"Mediators Inflammation"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322260","article-title":"Mucus barrier, mucins and gut microbiota: The expected slimy partners","volume":"69","author":"Paone","year":"2020","journal-title":"Gut"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316723","article-title":"Human gut microbiome: Hopes, threats and promises","volume":"67","author":"Cani","year":"2018","journal-title":"Gut"},{"key":"B124","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1038\/s41467-022-30240-8","article-title":"Gut microbiota regulates acute myeloid leukaemia via alteration of intestinal barrier function mediated by butyrate","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-026-04162-w","article-title":"Bone marrow adipose tissue in obesity: A previously underappreciated but promising therapeutic target","volume":"31","author":"Yu","year":"2026","journal-title":"Eur J Med Res"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2016.58928","article-title":"Obesity and inflammation: The linking mechanism and the complications","volume":"13","author":"Ellulu","year":"2017","journal-title":"Arch Med Sci"},{"key":"B127","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3945\/an.115.010207","article-title":"Impact of obesity and metabolic syndrome on immunity","volume":"7","author":"Andersen","year":"2016","journal-title":"Adv Nutr"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.594150","article-title":"Role of metabolic endotoxemia in systemic inflammation and potential interventions","volume":"11","author":"Mohammad","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1918955\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:23:25Z","timestamp":1788528205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1918955\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":128,"alternative-id":["10.3389\/fonc.2026.1918955"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1918955","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"article-number":"1918955"}}