title: TGFβ and IL10 have an impact on risk group and prognosis in childhood ALL.
abstract: 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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Hematology/Oncology and Stem Cell Transplantation, University of Würzburg, Children's Hospital, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Winkler
authors.forename: J
authors.initials: J
authors.lastname: Taschik
authors.forename: I
authors.initials: I
authors.lastname: Haubitz
authors.forename: M
authors.initials: M
authors.lastname: Eyrich
authors.forename: P G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: V
authors.initials: V
authors.lastname: Wiegering
mesh_terms: D016022:Case-Control Studies; D002648:Child; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: ALL; cytokine; paediatric; polymorphism; prognosis