Jevtovic-Stoimenov Tatjana, Kocic Gordana, Pavlovic Dusica, Macukanovic-Golubovic Lana, Marjanovic Goran, Djordjevic Vidosava, Tosić Natasa, Pavlović Sonja
Institute of Biochemistry, Medical Faculty University of Nis, Serbia and Montenegro.
Leuk Lymphoma. 2008 Nov;49(11):2163-9. doi: 10.1080/10428190802381220.
Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) have been shown to play an important role in the pathogenesis of limphoproliferative disease. Both cytokines regulate cell-survival and cell-death in leukemic cells. TNF-alpha and LT-alpha are highly produced in chronic lymphotic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients. Genetic polymorphism within regulatory regions of these cytokine genes can alter their expression levels. This study investigates an influence of TNF-alpha - 308 and LT-alpha + 250 polymorphisms on the activity of alkaline DNase in mononuclear cells of both patient groups as a potent biochemical marker of DNA fragmentation in the terminal phase of apoptosis. Study was performed on mononuclear cells of CLL and NHL patients. SNP were obtained by PCR-RFLP method. The activity of alkaline DNase was measured by spectrophotometric method. The study provided evidence of the influence of TNFG/A genotype and A alleles in the susceptibility to NHL, since the association of LT-alphaG/G genotype with CLL was observed. High-producing TNF-alpha - 308/LT-alpha + 250 heterozygous haplotype is associated with high NHL incidence. The investigated SNP influence the activity of alkaline DNase in CLL and NHL patients. The observed polymorphisms may modulate susceptibility of leukemic cells to apoptosis by way of DNase activity.
肿瘤坏死因子α（TNF-α）和淋巴毒素α（LT-α）已被证明在淋巴细胞增殖性疾病的发病机制中起重要作用。这两种细胞因子均调节白血病细胞的细胞存活和细胞死亡。TNF-α和LT-α在慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL）患者中大量产生。这些细胞因子基因调控区域内的基因多态性可改变其表达水平。本研究调查了TNF-α - 308和LT-α + 250基因多态性对两组患者单核细胞中碱性脱氧核糖核酸酶活性的影响，碱性脱氧核糖核酸酶活性是凋亡终末期DNA片段化的一种有效生化标志物。研究对象为CLL和NHL患者的单核细胞。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法获得单核苷酸多态性（SNP）。采用分光光度法测定碱性脱氧核糖核酸酶的活性。该研究提供了TNFG/A基因型和A等位基因对NHL易感性有影响的证据，因为观察到LT-αG/G基因型与CLL有关联。高产生TNF-α - 308/LT-α + 250杂合单倍型与高NHL发病率相关。所研究的SNP影响CLL和NHL患者碱性脱氧核糖核酸酶的活性。观察到的多态性可能通过脱氧核糖核酸酶活性调节白血病细胞对凋亡的易感性。
