Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging
Abstract
BACKGROUND: Large epidemiologic studies have reported the premature onset of age‐related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation. METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18‐35 years) who attended annual follow‐up clinic and compared with healthy, age‐matched and sex‐matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis. RESULTS: Survivors had significant elevation of plasma interleukin‐2 (IL‐2), IL‐10, IL‐17a, and high‐sensitivity C‐reactive protein levels (all P < .05). A raised high‐sensitivity C‐reactive protein level (>0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501‐35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013). CONCLUSIONS: Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age‐related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long‐term impact on overall health. Cancer 2017;123:4207–4214. © 2017 American Cancer Society.
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Childhood cancer survivors have premature accumulation of T lymphocytes expressing high levels of p16 INK4a and have higher circulating concentrations of the pro-inflammatory SASP factors IL-10 and IL-17.
“Childhood cancer survivors have premature accumulation of T lymphocytes expressing high levels of p16 INK4a and have higher circulating concentrations of the pro- inflammatory SASP factors IL-10 and IL-17 (refs. 193,197 ) .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [197]
Survivors of childhood cancers tend to develop chronic conditions such as cardiovascular dysfunction, ischaemic cardiac failure, renal and hepatic disorders, diabetes, poor fitness, muscular weakness and cognitive decline two decades earlier than individuals with no history of paediatric cancer treatment.
“Examples of such accelerated ageing pheno types have been observed in survivors of childhood cancers who are cured from their malignant diseases but tend to develop chronic conditions - such as cardiovascular dysfunction, ischaemic cardiac failure, renal and hepatic disorders, diabetes, poor fitness, muscular weakness and cognitive decline - two decades earlier than individuals with no history of”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [197]
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Senescence and cancer — role and therapeutic opportunities
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- Authors
- Ariffin, H., Azanan, M. S., Abd Ghafar, S. S., Oh, L., Lau, K. H., Thirunavakarasu, T., Sedan, A., Ibrahim, K., Chan, A., Chin, T. F., Liew, F. F., Jeyamogan, S., Rosli, E. S., Baharudin, R., Yap, T. Y., Skinner, R., Lum, S. H., & Hainaut, P.
- Affiliations
- University of Malaya (MY)
- Department of Pediatrics Faculty of Medicine, University of Malaya Kuala Lumpur Malaysia
- Royal Victoria Infirmary (GB)
- Institut pour l'avancée des biosciences (FR)
- Corresponding author
- Ariffin, Hany
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2017-06-27
- Volume
- 123
- Issue
- 21
- Pages
- 4207-4214
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W2732089561
- Cited by
- 99
- References
- 6
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 5 · 2018: 7
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Higher Education, Malaysia (UM.C/HIR/MOHE/MED/12)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- childhood acute lymphoblastic leukemia, cancer survivors, young adults, chronic inflammation, cellular aging, leukocyte telomere length, telomere shortening, inflammatory cytokines, C-reactive protein, interleukin-2, IL-10, IL-17A, metabolic syndrome, cranial irradiation, premature aging
- MeSH terms
- Adult Survivors of Child Adverse Events, Adolescent, Adult, Aging, C-Reactive Protein, Chronic Disease, Female, Humans, Inflammation, Interleukin-2, Interleukins, Male, Phenotype, Biomarkers, Case-Control Studies, Cranial Irradiation, Telomere, Interleukin-10, Cellular Senescence, Interleukin-17, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Young Adult, Telomere Shortening
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