{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:48:55Z","timestamp":1773272935162,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T00:00:00Z","timestamp":1411776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010risk acute lymphoblastic leukaemia (ALL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>In this study, we investigated the influence of cytokine gene polymorphisms (TNF\u03b1, TGF\u03b2, IL10 and IFN\u03b3) on frequency, risk group and prognosis in 95 paediatric ALL\u2010patients. We further report on intracellular production of these cytokines in T\u2010cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL10 high\u2010producer\u2010haplotypes were reduced in ALL\u2010patients compared with healthy controls and resulted in a reduced relapse rate compared with low\u2010producer haplotypes. TGF\u03b2 high\u2010producer\u2010haplotypes were correlated with a high initial blast\u2010count (codon 25: G\/G) and were elevated in high\u2010risk ALL\u2010patients (codon 10: T\/T).<\/jats:p><jats:p>IL10 was positively and IFN\u03b3\u2010production was negatively correlated with initial blast\u2010count. At diagnosis the expression of TNF\u03b1 and IFN\u03b3 was reduced in patients compared with healthy controls. This was more pronounced in high\u2010risk and in T\u2010ALL\u2010patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that gene\u2010polymorphisms of the regulatory\/anti\u2010inflammatory cytokines, TGF\u03b2 and IL10, but not of the pro\u2010inflammatory cytokines, IFN\u03b3 and TNF\u03b1, have an impact on prognosis and risk\u2010group of ALL. However, the reduced capacity to produce pro\u2010inflammatory cytokines at diagnosis may serve as another important, functional risk factor. These data may help in further risk stratification and adaptation of therapy\u2010intensity in paediatric patients with ALL. Pediatr Blood Cancer 2015;62:72\u201379. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25142","type":"journal-article","created":{"date-parts":[[2014,9,28]],"date-time":"2014-09-28T02:07:15Z","timestamp":1411870035000},"page":"72-79","source":"Crossref","is-referenced-by-count":14,"title":["TGF\u03b2 and IL10 have an impact on risk group and prognosis in childhood ALL"],"prefix":"10.1002","volume":"62","author":[{"given":"B.","family":"Winkler","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University of W\u00fcrzburg, Children's Hospital Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Taschik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University of W\u00fcrzburg, Children's Hospital Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Haubitz","sequence":"additional","affiliation":[{"name":"Department of Biometry University of W\u00fcrzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Eyrich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University of W\u00fcrzburg, Children's Hospital Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.G.","family":"Schlegel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University of W\u00fcrzburg, Children's Hospital Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Wiegering","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University of W\u00fcrzburg, Children's Hospital Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60457-2"},{"key":"e_1_2_5_3_1","first-page":"3310","article-title":"Improved outcome in childhood acute lymphoblastic leukaemia despite reduced use of anthracyclines and cranial radiotherapy: Results of trial ALL\u2010BFM 90. 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