TGFβ and IL10 Have an Impact on Risk Group and Prognosis in Childhood ALL

BackgroundCytokines 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). ProcedureIn this study, we investigated the influence of cytokine gene polymorphisms (TNF, TGF, IL10 and IFN) on frequency, risk group and prognosis in 95 paediatric ALL-patients. We further report on intracellular production of these cytokines in T-cells. ResultsIL10 high-producer-haplotypes were reduced in ALL-patients compared with healthy controls and resulted in a reduced relapse rate compared with low-producer haplotypes. TGF 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 IFN-production was negatively correlated with initial blast-count. At diagnosis the expression of TNF and IFN was reduced in patients compared with healthy controls. This was more pronounced in high-risk and in T-ALL-patients. ConclusionWe conclude that gene-polymorphisms of the regulatory/anti-inflammatory cytokines, TGF and IL10, but not of the pro-inflammatory cytokines, IFN and TNF, 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. Pediatr Blood Cancer 2015;62:72-79. (c) 2014 Wiley Periodicals, Inc.