%0 Journal Article
%T Influence of IL10 (G1082A) and TNF¦Á (G308A) Polymorphisms on the Survival of Pediatric Patients with ALL
%A Dayse Maria Vasconcelos de Deus
%A Karina Ara¨²jo Lugo
%A Maria Tereza Cartaxo Muniz
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/692348
%X Interleukin 10 (IL10) is a pleiotropic cytokine that stimulates various hematopoietic cells. The tumor necrosis factor alpha (TNF¦Á) is a cytokine that may influence the transcriptional activity induced by glucocorticoids. This study examined the impact of TNF¦Á (G308A) and IL10 (G1082A) polymorphisms at promoter regions in relation to the overall survival of 105 children years) with acute lymphoblastic leukemia (ALL) for a period of 126 months, treated according to the protocol GBTLI99. The G1082A and G308A polymorphisms were identified by allele-specific PCR and PCR-RFLP, respectively. Patients with IL10AA genotype had a higher death ratio (44%, . Patients with both IL10AA and TNFAA genotypes showed the worst survival when compared with the IL10GG and TNFGA genotypes ( . The results of this study revealed a lower survival among patients with IL10AA genotype and the concomitant occurrence of IL10AA and TNFAA genotypes. 1. Introduction Glucocorticoids were among the first drug classes used in the treatment of patients with ALL and are still essential components of treatment [1]. The glucocorticoid receptors (GR) can form dimers, translocate to the nucleus, and interact with glucocorticoid-response elements to transactivate gene expression, or they can remain as monomers and repress the activity of transcription factors such as the activating protein-1 (AP-1) and nuclear factor- B (NF B) [2]. Traditionally, prednisone has been the glucocorticoid¡¯s most commonly used drug in the treatment of patients with acute lymphoblastic leukemia (ALL). It is typically given for 4 consecutive weeks in combination with vincristine, anthracycline, asparaginase, and intrathecal chemotherapy. In the past few years, dexamethasone, another glucocorticoid, has been increasingly used to treat ALL. The biological background of prednisone response is still unknown. However, there have been investigations with respect to glucocorticoid receptors [3], distribution of GR isoforms [4], and genetic polymorphisms [5]. Polymorphisms at the promoter region of IL10 gene are associated with several diseases, including autoimmune, infectious, cancer, Alzheimer¡¯s disease (AD), and lymphoblastic leukemia [6]. Subsequently, pleiotropic inhibitory and stimulatory effects on various types of blood cells were described for IL-10, including its role as a survival and differentiation factor for B cells. IL10 is produced by activated monocytes and T cells [7]. A polymorphism at -1082 position, within the IL-10 gene promoter region, is known to have an influence on IL-10 plasma levels. The homozygous
%U http://www.hindawi.com/journals/lrt/2012/692348/