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TGFβ and IL10 have an impact on risk group and prognosis in childhood ALL
B Winkler1, J Taschik, I Haubitz
1Department of Pediatric Hematology/Oncology and Stem Cell Transplantation, University of Würzburg, Children's Hospital, Germany.
Insights
Cytokine gene variations in Interleukin-10 (IL10) and Transforming Growth Factor-beta (TGFβ) impact prognosis in pediatric acute lymphoblastic leukemia (ALL). Reduced pro-inflammatory cytokine production is also a risk factor.
Area of Science:
- Immunogenetics
- Pediatric Oncology
- Molecular Biology
Background:
- Cytokines and their genes influence disease outcomes in various conditions, including cancer.
- Previous research established the link between cytokine production and prognosis in pediatric acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To investigate the association between cytokine gene polymorphisms (TNFα, TGFβ, IL10, IFNγ) and the frequency, risk group, and prognosis of pediatric ALL.
- To analyze intracellular cytokine production in T-cells among these patients.
Main Methods:
- Study included 95 pediatric ALL patients.
- Analyzed polymorphisms in TNFα, TGFβ, IL10, and IFNγ genes.
- Assessed intracellular cytokine production in T-cells.
Main Results:
- IL10 high-producer haplotypes were less common in ALL patients and associated with lower relapse rates.
- TGFβ high-producer haplotypes correlated with higher blast counts and were elevated in high-risk ALL.
- Reduced expression of TNFα and IFNγ was observed in ALL patients at diagnosis, particularly in high-risk and T-ALL cases.
Conclusions:
- Gene polymorphisms in regulatory cytokines TGFβ and IL10, but not pro-inflammatory IFNγ and TNFα, affect ALL prognosis and risk stratification.
- Reduced pro-inflammatory cytokine production capacity at diagnosis is a significant functional risk factor.
- Findings may aid in refining risk assessment and tailoring therapy intensity for pediatric ALL patients.
Background:
Cytokines and their genes have been described to have an influence on incidence and prognosis in malignant, infectious and autoimmune disease. We previously described the impact of cytokine production on prognosis in paediatric standard-risk acute lymphoblastic leukaemia (ALL).
Procedure:
In this study, we investigated the influence of cytokine gene polymorphisms (TNFα, TGFβ, IL10 and IFNγ) on frequency, risk group and prognosis in 95 paediatric ALL-patients. We further report on intracellular production of these cytokines in T-cells.
Results:
IL10 high-producer-haplotypes were reduced in ALL-patients compared with healthy controls and resulted in a reduced relapse rate compared with low-producer haplotypes. TGFβ high-producer-haplotypes were correlated with a high initial blast-count (codon 25: G/G) and were elevated in high-risk ALL-patients (codon 10: T/T). IL10 was positively and IFNγ-production was negatively correlated with initial blast-count. At diagnosis the expression of TNFα and IFNγ was reduced in patients compared with healthy controls. This was more pronounced in high-risk and in T-ALL-patients.
Conclusion:
We conclude that gene-polymorphisms of the regulatory/anti-inflammatory cytokines, TGFβ and IL10, but not of the pro-inflammatory cytokines, IFNγ and TNFα, have an impact on prognosis and risk-group of ALL. However, the reduced capacity to produce pro-inflammatory cytokines at diagnosis may serve as another important, functional risk factor. These data may help in further risk stratification and adaptation of therapy-intensity in paediatric patients with ALL.
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