Lauten M, Matthias T, Stanulla M, Beger C, Welte K, Schrappe M
Hannover Medical School, Children's Hospital, Department of Paediatric Haematology and Oncology, Hannover, Germany.
Leukemia. 2002 Aug;16(8):1437-42. doi: 10.1038/sj.leu.2402545.
Plasma levels of TNF and IL-10 have been associated with therapy outcome in haematological malignancies and are influenced by genetic variation due to germline polymorphisms within the TNF and IL-10 genes. Different TNF and IL-10 genetic polymorphisms might therefore also correlate with clinical outcome in childhood acute lymphoblastic leukaemia (ALL). We analysed the association of TNF and IL-10 polymorphisms with response to initial treatment and risk of relapse in 135 children with ALL, treated according to Berlin-Frankfurt-Münster (BFM) protocols. Our data showed a protective effect from prednisone poor response in patients with the IL-10 G/G genotype, whereas no association of the risk of relapse and IL-10 genotype was found. In the total study group, subjects expressing the TNF2 allele neither showed a statistically significant general association with prednisone response nor with risk of relapse compared to subjects homozygous for the TNF1 allele. Nevertheless, we did find a higher risk of relapse in poor prednisone responders expressing the TNF2 allele compared to poor prednisone responders not expressing the TNF2 allele. We conclude that IL-10 genotype might influence prednisone response in patients with childhood ALL, whereas TNF genotype seems to influence the risk of relapse in high risk ALL patients.
肿瘤坏死因子（TNF）和白细胞介素-10（IL-10）的血浆水平与血液系统恶性肿瘤的治疗结果相关，并且受TNF和IL-10基因种系多态性导致的基因变异影响。因此，不同的TNF和IL-10基因多态性也可能与儿童急性淋巴细胞白血病（ALL）的临床结果相关。我们分析了135例按照柏林-法兰克福-明斯特（BFM）方案治疗的ALL儿童中，TNF和IL-10多态性与初始治疗反应及复发风险的相关性。我们的数据显示，IL-10 G/G基因型患者对泼尼松反应不佳有保护作用，而未发现复发风险与IL-10基因型有关联。在整个研究组中，与TNF1等位基因纯合子受试者相比，表达TNF2等位基因的受试者与泼尼松反应或复发风险均未显示出统计学上的显著总体关联。然而，我们确实发现，与未表达TNF2等位基因的泼尼松反应不佳者相比，表达TNF2等位基因的泼尼松反应不佳者复发风险更高。我们得出结论，IL-10基因型可能影响儿童ALL患者对泼尼松的反应，而TNF基因型似乎影响高危ALL患者的复发风险。
