Startseite Evaluating obesity and fat cells as possible important metabolic players in childhood leukemia
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Evaluating obesity and fat cells as possible important metabolic players in childhood leukemia

  • Isabela Sallati , Julia Abend Bardagi , José Alexandre Mendonça und Giovanna R. Degasperi ORCID logo EMAIL logo
Veröffentlicht/Copyright: 29. April 2025
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 38 Heft 8

Abstract

Introduction

The prevalence of overweight and obesity in childhood is a health challenge. This condition induces alterations in adipose tissue and metabolic disorders such as diabetes, dyslipidemia, and hypertension even in childhood and may also be associated with cancer development. Underlying mechanisms related to childhood cancer, such as leukemia and obesity, are not entirely understood.

Content

Considering this scenario, a systematic literature review was performed on the PubMed library. Studies that evaluate the association between overweight or obesity at diagnosis of childhood leukemia and the outcomes associated with this condition were included.

Summary

In some studies, a worse prognosis was observed in obese children compared to non-obese, which begs the question of how the adipose tissue environment may be involved with leukemia progression and its outcomes such as relapse, overall and event-free survival and infections.

Outlook

Obesity in children diagnosed with leukemia may be associated with poor outcomes during disease progression as reported in some studies. The remodeling and composition of adipose tissue, alterations in adipocytokines secretion, such as leptin, and inflammation that may trigger awakened oncogenes seem to be important players in cancer development and outcomes during treatment. Understanding if there is any relationship between adipose tissue and the development of childhood leukemia and its prognosis, as well as the biological mechanisms of this scenario, is important to contribute to improving the treatment protocols and survival, especially in obese children.

Keywords: childhood leukemia; childhood obesity; adipose tissue; body mass index; outcomes
Corresponding author: Giovanna R. Degasperi, School of Life Sciences, Pontifical Catholic University of Campinas, Campinas, SP, Brazil; and Postgraduate Program in Health Sciences – Pontifical Catholic University of Campinas, Av. John Boyd Dunlop – Jardim Ipaussurama, Campinas, SP, 13034-685, Brazil, E-mail:
Isabela Sallati and Julia Abend Bardagi contributed equally to this work.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: G.D. was responsible for conception and design. J.A.M. was responsible for including the risk of bias. I.S. and J.A.B. performed the data collection and organization of tables and references. The analysis was conducted by G.D., I.S., and J.A.B. Professors G.D. and J.A.B. were responsible for advising in case of disagreement between the other authors during the article selection and data extraction. All authors contributed to the final review of the manuscript.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. GBD 2021 US Obesity Forecasting Collaborators. National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990–2021, and forecasts up to 2050. Lancet 2024;404:2278–98. https://doi.org/10.1016/S0140-6736(24)01548-4.Suche in Google Scholar PubMed PubMed Central

2. Liu, S, Hu, B, Zhang, J. Epidemiological characteristics and influencing factors of acute leukemia in children and adolescents and adults: a large population-based study. Hematology 2024;29:2327916. https://doi.org/10.1080/16078454.2024.2327916.Suche in Google Scholar PubMed

3. Mohammadian-Hafshejani, A, Farber, IM, Kheiri, S. Global incidence and mortality of childhood leukemia and its relationship with the Human Development Index. PLoS One 2024;19:e0304354. https://doi.org/10.1371/journal.pone.0304354.Suche in Google Scholar PubMed PubMed Central

4. Du, M, Chen, W, Liu, K, Wang, L, Hu, Y, Mao, Y, et al.. The global burden of leukemia and its attributable factors in 204 countries and territories: findings from the Global Burden of Disease 2019 study and projections to 2030. JAMA Oncol 2022;2022:1612702. https://doi.org/10.1155/2022/1612702.Suche in Google Scholar PubMed PubMed Central

5. Malard, F, Mohty, M. Acute lymphoblastic leukaemia. Lancet 2020;395:1146–62. https://doi.org/10.1016/s0140-6736(19)33018-1.Suche in Google Scholar

6. Creutzig, U, Kutny, MA, Barr, R, Schlenk, RF, Ribeiro, RC. Acute myelogenous leukemia in adolescents and young adults. Pediatr Blood Cancer 2018;65:e27089. https://doi.org/10.1002/pbc.27089.Suche in Google Scholar PubMed PubMed Central

7. Bhojwani, D, Yang, JJ, Pui, CH. Biology of childhood acute lymphoblastic leukemia. Pediatr Clin 2015;62:47–60. https://doi.org/10.1016/j.pcl.2014.09.004.Suche in Google Scholar PubMed PubMed Central

8. Taga, T, Tomizawa, D, Takahashi, H, Adachi, S. Acute myeloid leukemia in children: current status and future directions. Pediatr Int 2016;58:71–80. https://doi.org/10.1111/ped.12865.Suche in Google Scholar PubMed

9. Hjalgrim, LL, Westergaard, T, Rostgaard, K, Schmiegelow, K, Melbye, M, Hjalgrim, H, et al.. Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 2003;158:724–35. https://doi.org/10.1093/aje/kwg210.Suche in Google Scholar PubMed

10. Heslehurst, N, Vieira, R, Akhter, Z, Bailey, H, Slack, E, Ngongalah, L, et al.. The association between maternal body mass index and child obesity: a systematic review and meta-analysis. PLoS Med 2019;16:e1002817. https://doi.org/10.1371/journal.pmed.1002817.Suche in Google Scholar PubMed PubMed Central

11. Stacy, SL, Buchanich, JM, Ma, ZQ, Mair, C, Robertson, L, Sharma, RK, et al.. Maternal obesity, birth size, and risk of childhood cancer development. Am J Epidemiol 2019;188:1503–11. https://doi.org/10.1093/aje/kwz118.Suche in Google Scholar PubMed PubMed Central

12. Fisher, JO, Birch, LL. Eating in the absence of hunger and overweight in girls from 5 to 7 years of age. Am J Clin Nutr 2002;75:226–31.10.1093/ajcn/76.1.226Suche in Google Scholar PubMed PubMed Central

13. Lee, EY, Kang, B, Yang, Y, Yang, HK, Kim, HS, Lim, SY, et al.. Study time after school and habitual eating are associated with risk for obesity among overweight Korean children: a prospective study. Obes Facts 2018;11:46–55. https://doi.org/10.1159/000486132.Suche in Google Scholar PubMed PubMed Central

14. Headid, RJ, Park, SY. The impacts of exercise on pediatric obesity. Clin Exp Pediatr 2021;64:196–207. https://doi.org/10.3345/cep.2020.00997.Suche in Google Scholar PubMed PubMed Central

15. Cioana, M, Deng, J, Nadarajah, A, Hou, M, Qiu, Y, Chen, SSJ, et al.. The prevalence of obesity among children with type 2 diabetes: a systematic review and meta-analysis. JAMA Netw Open 2022;5:e2247186. https://doi.org/10.1001/jamanetworkopen.2022.47186.Suche in Google Scholar PubMed PubMed Central

16. Gepstein, V, Weiss, R. Obesity as the main risk factor for metabolic syndrome in children. Front Endocrinol 2019;10:568. https://doi.org/10.3389/fendo.2019.00568.Suche in Google Scholar PubMed PubMed Central

17. Ding, N, Zhan, J, Shi, Y, Qiao, T, Li, P, Zhang, T. Obesity in children and adolescents and the risk of ovarian cancer: a systematic review and dose-response meta-analysis. PLoS One 2022;17:e0278050. https://doi.org/10.1371/journal.pone.0278050.Suche in Google Scholar PubMed PubMed Central

18. Mohammadian Khonsari, N, Shahrestanaki, E, Ehsani, A, Asadi, S, Sokoty, L, Mohammadpoor Nami, S, et al.. Association of childhood and adolescence obesity with incidence and mortality of adulthood cancers: a systematic review and meta-analysis. Front Endocrinol 2023;14:1069164. https://doi.org/10.3389/fendo.2023.1069164.Suche in Google Scholar PubMed PubMed Central

19. Liberati, A, Altman, DG, Tetzlaff, J, Mulrow, C, Gøtzsche, PC, Ioannidis, JP, et al.. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e1–34. https://doi.org/10.1371/journal.pmed.1000100.Suche in Google Scholar PubMed PubMed Central

20. Page, MJ, Moher, D, Bossuyt, PM, Boutron, I, Hoffmann, TC, Mulrow, CD, et al.. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. Br Med J 2021;372:n60. https://doi.org/10.1136/bmj.n160.Suche in Google Scholar PubMed PubMed Central

21. Sterne, JAC, Hernán, MA, Reeves, BC, Savović, J, Berkman, ND, Viswanathan, M, et al.. ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions. Br Med J 2016;355:i4919.10.1136/bmj.i4919Suche in Google Scholar PubMed PubMed Central

22. Heymsfield, SB, Peterson, CM, Thomas, DM, Heo, M, Schuna, JM. Why are there race/ethnic differences in adult body mass index-adiposity relationships? A quantitative critical review. Obes Rev 2016;17:262–75. https://doi.org/10.1111/obr.12358.Suche in Google Scholar PubMed PubMed Central

23. Hu, W, Cheung, YT, Tang, Y, Hong, L, Zhu, Y, Chen, J, et al.. Association between body mass index at diagnosis and outcomes in Chinese children with newly diagnosed acute lymphoblastic leukemia. Cancer Med 2023;12:2850–60. https://doi.org/10.1002/cam4.5188.Suche in Google Scholar PubMed PubMed Central

24. Galati, PC, Rocha, PRS, Gruezo, ND, Amato, AA. Body mass trajectory from diagnosis to the end of treatment in a pediatric acute lymphoblastic leukemia cohort. Sci Rep 2023;13:13590. https://doi.org/10.1038/s41598-023-39287-z.Suche in Google Scholar PubMed PubMed Central

25. Jaime-Pérez, JC, Turrubiates-Hernández, GA, García-Salas, G, de la Torre-Salinas, AM, Áncer-Rodríguez, P, Villarreal-Martínez, L, et al.. The influence of nutritional status at diagnosis of childhood B-cell acute lymphoblastic leukemia on survival rates: data from a Hispanic cohort. Nutr Cancer 2022;74:889–95. https://doi.org/10.1080/01635581.2021.1934042.Suche in Google Scholar PubMed

26. Egnell, C, Ranta, S, Banerjee, J, Merker, A, Niinimäki, R, Lund, B, et al.. Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols. Eur J Haematol 2020;105:797–807. https://doi.org/10.1111/ejh.13517.Suche in Google Scholar PubMed PubMed Central

27. Meenan, CK, Kelly, JA, Wang, L, Ritchey, AK, Maurer, SH. Obesity in pediatric patients with acute lymphoblastic leukemia increases the risk of adverse events during pre-maintenance chemotherapy. Pediatr Blood Cancer 2019;66:e27515. https://doi.org/10.1002/pbc.27515.Suche in Google Scholar PubMed PubMed Central

28. Núñez-Enríquez, JC, Gil-Hernández, AE, Jiménez-Hernández, E, Fajardo-Gutiérrez, A, Medina-Sansón, A, Flores-Lujano, J, et al.. Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study. BMC Cancer 2019;19:708. https://doi.org/10.1186/s12885-019-5878-8.Suche in Google Scholar PubMed PubMed Central

29. Saenz, AM, Stapleton, S, Hernandez, RG, Hale, GA, Goldenberg, NA, Schwartz, S, et al.. Body mass index at pediatric leukemia diagnosis and the risks of relapse and mortality: findings from a single institution and meta-analysis. J Obes 2018;2018:7048078. https://doi.org/10.1155/2018/7048078.Suche in Google Scholar PubMed PubMed Central

30. Eissa, HM, Zhou, Y, Panetta, JC, Browne, EK, Jeha, S, Cheng, C, et al.. The effect of body mass index at diagnosis on clinical outcome in children with newly diagnosed acute lymphoblastic leukemia. Blood Cancer J 2017;7. https://doi.org/10.1038/bcj.2017.11.Suche in Google Scholar PubMed PubMed Central

31. Orgel, E, Tucci, J, Alhushki, W, Malvar, J, Sposto, R, Fu, CH, et al.. Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia. Blood 2014;124:3932–8. https://doi.org/10.1182/blood-2014-08-595389.Suche in Google Scholar PubMed

32. Aldhafiri, FK, McColl, JH, Reilly, JJ. Prognostic significance of being overweight and obese at diagnosis in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2014;36:234–6. https://doi.org/10.1097/mph.0000000000000056.Suche in Google Scholar PubMed

33. Suchacki, KJ, Tavares, AAS, Mattiucci, D, Scheller, EL, Papanastasiou, G, Gray, C, et al.. Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nat Commun 2020;11:3097. https://doi.org/10.1038/s41467-020-16878-2.Suche in Google Scholar PubMed PubMed Central

34. Whiteley, AE, Price, TT, Cantelli, G, Sipkins, DA. Leukaemia: a model metastatic disease. Nat Rev Cancer 2021;21:461–75. https://doi.org/10.1038/s41568-021-00355-z.Suche in Google Scholar PubMed PubMed Central

35. Tucci, J, Chen, T, Margulis, M, Orgel, E, Paszkiewicz, RL, Cohen, MD, et al.. Adipocytes provide fatty acids to acute lymphoblastic leukemia cells. Front Oncol 2021;11:665763. https://doi.org/10.3389/fonc.2021.665763.Suche in Google Scholar PubMed PubMed Central

36. Kumar, B, Orellana, M, Brooks, J, Madabushi, SS, Vishwasrao, P, Parra, LE, et al.. Exosomes-driven lipolysis and bone marrow niche remodeling supports leukemia expansion. Haematologica 2020;106:1484–8. https://doi.org/10.3324/haematol.2019.246058.Suche in Google Scholar PubMed PubMed Central

37. Sheng, X, Parmentier, JH, Tucci, J, Pei, H, Cortez-Toledo, O, Dieli-Conwright, CM, et al.. Adipocytes sequester and metabolize the chemotherapeutic daunorubicin. Mol Cancer Res 2017;15:1704–13. https://doi.org/10.1158/1541-7786.mcr-17-0338.Suche in Google Scholar PubMed PubMed Central

38. Tobin, LM, Mavinkurve, M, Carolan, E, Kinlen, D, O’Brien, EC, Little, MA, et al.. NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient. JCI Insight 2017;2:e94939. https://doi.org/10.1172/jci.insight.94939.Suche in Google Scholar PubMed PubMed Central

39. Torelli, GF, Peragine, N, Raponi, S, Pagliara, D, De Propris, MS, Vitale, A, et al.. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells. Haematologica 2014;99:1248–54. https://doi.org/10.3324/haematol.2013.101931.Suche in Google Scholar PubMed PubMed Central

40. Coënon, L, Geindreau, M, Ghiringhelli, F, Villalba, M, Bruchard, M. Natural killer cells at the frontline in the fight against cancer. Cell Death Dis 2024;15:614. https://doi.org/10.1038/s41419-024-06976-0.Suche in Google Scholar PubMed PubMed Central

41. Zahran, AM, Shibl, A, Rayan, A, Mohamed, MAEH, Osman, AMM, Saad, K, et al.. Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia. Sci Rep 2021;11:15039. https://doi.org/10.1038/s41598-021-94469-x.Suche in Google Scholar PubMed PubMed Central

42. Xu, S, Chaudhary, O, Rodríguez-Morales, P, Sun, X, Chen, D, Zappasodi, R, et al.. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Immunity 2021;54:1561–77. https://doi.org/10.1016/j.immuni.2021.05.003.Suche in Google Scholar PubMed PubMed Central

43. Dyck, L, Prendeville, H, Raverdeau, M, Wilk, MM, Loftus, RM, Douglas, A, et al.. Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function. J Exp Med 2022;219:e20210042. https://doi.org/10.1084/jem.20210042.Suche in Google Scholar PubMed PubMed Central

44. Friedman, JM. Leptin and the endocrine control of energy balance. Nat Metab 2019;1:754–64. https://doi.org/10.1038/s42255-019-0095-y.Suche in Google Scholar PubMed

45. Kyoung, AH, Il Ran, IR, Mi Jung, MJ, Jae Heon, JH, Churl Young, CY. Serum leptin levels in obese children. J Korean Pediatr Soc 1998;41:953–9.Suche in Google Scholar

46. Jaramillo-Ospina, Á, Castaño-Moreno, E, Muñoz-Muñoz, E, Krause, BJ, Uauy, R, Casanello, P, et al.. Maternal obesity is associated with higher cord blood adipokines in offspring most notably in females. J Pediatr Gastroenterol Nutr 2021;73:264–70. https://doi.org/10.1097/mpg.0000000000003172.Suche in Google Scholar

47. Caruso, A, Gelsomino, L, Panza, S, Accattatis, FM, Naimo, GD, Barone, I, et al.. Leptin: a heavyweight player in obesity-related cancers. Biomolecules 2023;13:1084. https://doi.org/10.3390/biom13071084.Suche in Google Scholar PubMed PubMed Central

48. Papathanassoglou, E, El-Haschimi, K, Li, XC, Matarese, G, Strom, T, Mantzoros, C. Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J Immunol 2006;176:7745–52. https://doi.org/10.4049/jimmunol.176.12.7745.Suche in Google Scholar PubMed

49. Martín-Romero, C, Santos-Alvarez, J, Goberna, R, Sánchez-Margalet, V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol 2000;199:15–24. https://doi.org/10.1006/cimm.1999.1594.Suche in Google Scholar PubMed

50. Nakao, T, Hino, M, Yamane, T, Nishizawa, Y, Morii, H, Tatsumi, N. Expression of the leptin receptor in human leukaemic blast cells. Br J Haematol 1998;102:740–5. https://doi.org/10.1046/j.1365-2141.1998.00843.x.Suche in Google Scholar PubMed

51. Hino, M, Nakao, T, Yamane, T, Ohta, K, Takubo, T, Tatsumi, N. Leptin receptor and leukemia. Leuk Lymphoma 2000;36:457–61. https://doi.org/10.3109/10428190009148392.Suche in Google Scholar PubMed

52. Lu, Z, Xie, J, Wu, G, Shen, J, Collins, R, Chen, W, et al.. Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. Nat Med 2017;23:79–90. https://doi.org/10.1038/nm.4252.Suche in Google Scholar PubMed PubMed Central

Received: 2024-09-17
Accepted: 2025-03-23
Published Online: 2025-04-29
Published in Print: 2025-08-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Endocrine treatment in Duchenne muscular dystrophy – current practices and future directions
  4. Reviews
  5. Pubertal induction therapy in pediatric patients with Duchenne muscular dystrophy
  6. Evaluating obesity and fat cells as possible important metabolic players in childhood leukemia
  7. Biological effects of recombinant human growth hormone therapy on metabolism in children with growth hormone deficiency: a review
  8. Original Articles
  9. The use of bisphosphonate and testosterone in young people with Duchenne muscular dystrophy: an international clinician survey
  10. Characterizing the metabolome of children with growth hormone deficiency
  11. Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?
  12. Comparison of the clinical characteristics of children with Silver–Russell syndrome genetically confirmed or not and their response to growth hormone therapy: a national multicenter study
  13. Testicular adrenal rest tumors in Indonesian boys with congenital adrenal hyperplasia
  14. Oxidative stress in branched-chain organic acidemias using thiol-disulfide homeostasis
  15. Case Reports
  16. Delayed diagnosis of retroperitoneal paraganglioma in an 8-year-old boy with persistent hypertension: a case report and review of diagnostic challenges in pediatric secondary hypertension
  17. Pediatric iatrogenic Cushing’s syndrome: a series of seven cases induced by topical corticosteroid use
  18. Wolcott–Rallison syndrome: late-onset diabetes, multiple epiphyseal dysplasia, and acute liver failure – a case report
https://doi.org/10.1515/jpem-2024-0448
Schlagwörter für diesen Artikel
childhood leukemia; childhood obesity; adipose tissue; body mass index; outcomes

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Endocrine treatment in Duchenne muscular dystrophy – current practices and future directions
  4. Reviews
  5. Pubertal induction therapy in pediatric patients with Duchenne muscular dystrophy
  6. Evaluating obesity and fat cells as possible important metabolic players in childhood leukemia
  7. Biological effects of recombinant human growth hormone therapy on metabolism in children with growth hormone deficiency: a review
  8. Original Articles
  9. The use of bisphosphonate and testosterone in young people with Duchenne muscular dystrophy: an international clinician survey
  10. Characterizing the metabolome of children with growth hormone deficiency
  11. Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?
  12. Comparison of the clinical characteristics of children with Silver–Russell syndrome genetically confirmed or not and their response to growth hormone therapy: a national multicenter study
  13. Testicular adrenal rest tumors in Indonesian boys with congenital adrenal hyperplasia
  14. Oxidative stress in branched-chain organic acidemias using thiol-disulfide homeostasis
  15. Case Reports
  16. Delayed diagnosis of retroperitoneal paraganglioma in an 8-year-old boy with persistent hypertension: a case report and review of diagnostic challenges in pediatric secondary hypertension
  17. Pediatric iatrogenic Cushing’s syndrome: a series of seven cases induced by topical corticosteroid use
  18. Wolcott–Rallison syndrome: late-onset diabetes, multiple epiphyseal dysplasia, and acute liver failure – a case report
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 12.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jpem-2024-0448/html?lang=de
Button zum nach oben scrollen