Polymorphisms of tumor-necrosis factor-alpha - 308 and lymphotoxin-alpha + 250: possible modulation of susceptibility to apoptosis in chronic lymphocytic leukemia and non-Hodgkin lymphoma mononuclear cells.
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.
Jevtovic-Stoimenov
Tatjana
T
Institute of Biochemistry, Medical Faculty University of Nis, Serbia and Montenegro. tjevtovic@yahoo.com
Kocic
Gordana
G
Pavlovic
Dusica
D
Macukanovic-Golubovic
Lana
L
Marjanovic
Goran
G
Djordjevic
Vidosava
V
Tosić
Natasa
N
Pavlović
Sonja
S
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D003851:Deoxyribonucleases