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

Introduction: Considering that cytokines play an important role in immune response and that many infectious, autoimmune and malignant diseases are influenced by cytokine production, we hypothesized that genetically determined cytokine gene polymorphism might have an important influence on prognosis in pediatrics acute lymphoblastic leukemia (ALL).

Methods: In this study, 95 pediatric ALL-patients were examined with regard to cytokine gene polymorphisms (TNFα, TGFβ, IL10 and IFNγ) and their potential association with prognosis. Moreover we analyzed the intracellular production of theses cytokines in patient T-cells.

Results: TGFβ high-producer-haplotypes were associated with high-risk ALL-patients (Codon 10: T/T) and with the tendency of a reduced overall survival, whereas IL10 high-producer-genotypes were associated with a reduced relapse rate and a superior overall survival compared to IL-10-low-producer patients. Gene-polymorphisms of the pro-inflammatory cytokines IFNγ and TNFα did not show an impact on prognosis and risk-group of ALL in our cohort. On a functional basis TNFα and IFNγ expression of T-cells at initial diagnosis was significantly reduced in high-risk- and T-ALL-patients in comparison to healthy controls.

Summary: Cytokine gene-polymorphisms of the regulatory/anti-inflammatory cytokines TGFβ and IL10, but not of the pro-inflammatory cytokines IFNγ and TNFα seem to have an impact on prognosis of pediatric ALL patients. Reduced capacity to produce pro-inflammatory cytokines at diagnosis may serve as a functional risk factor. These data may help in further risk stratification and adaptation of therapy-intensity.