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Cytokine Levels at Birth in Children Who Developed Acute Lymphoblastic Leukemia
Todd P Whitehead1, Joseph L Wiemels2, Mi Zhou3
1School of Public Health, University of California, Berkeley, Berkeley, California. toddpwhitehead@berkeley.edu.
Insights
Children born with higher cytokine levels may have an increased risk of acute lymphoblastic leukemia (ALL). This study analyzed seven cytokines in newborn blood spots, finding elevated levels in ALL cases, particularly among certain demographics.
Area of Science:
- Immunology
- Pediatric Oncology
- Epidemiology
Background:
- Prenatal immune development is a potential factor in childhood acute lymphoblastic leukemia (ALL) etiology.
- Altered immune responses in early life may influence cancer risk.
- Understanding early immune markers is crucial for identifying at-risk populations.
Purpose of the Study:
- To investigate the association between cord blood cytokine levels at birth and the risk of childhood ALL.
- To explore potential mediating roles of cytokines in the relationship between neonatal metabolites and ALL.
- To examine disparities in cytokine levels and ALL risk among different demographic groups.
Main Methods:
- Analyzed seven cytokines (IL1β, IL4, IL6, IL8, GM-CSF, TNFα, VEGF) in newborn blood spots from 1,020 ALL cases and 1,003 controls.
- Used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for cytokine levels.
- Adjusted for sociodemographic and birth characteristics.
Main Results:
- Elevated levels of IL1β, IL8, TNFα, and VEGF were observed in newborns who later developed ALL.
- Higher cytokine levels were particularly associated with increased ALL risk in children of Latina mothers and for high hyperdiploidy ALL.
- Neonatal cytokine levels correlated with neonatal metabolites previously linked to ALL, but mediation was not evident.
Conclusions:
- Children born with altered cytokine profiles may be predisposed to aberrant immune reactions initiating ALL.
- This study highlights the potential role of prenatal immune system alterations in childhood ALL development.
- Findings suggest that early immune markers could inform future risk assessment strategies for childhood leukemia.
Background:
Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL).
Methods:
Seven cytokines, IL1β, IL4, IL6, IL8, GM-CSF, TNFα, and VEGF, were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. ORs and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression, adjusting for sociodemographic and birth characteristics.
Results:
We found that patients with ALL were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% confidence interval [CI], 1.03-1.35); IL8: 1.19 (1.03-1.38); TNFα: 1.15 (1.01-1.30); VEGF: 1.16 (1.01-1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk.
Conclusions:
We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL.
Impact:
This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.
