The relationship between oxidative stress and cytogenetic abnormalities in B-cell chronic lymphocytic leukemia
Tatiana Zhevak1, Tatiana Shelekhova2, Nina Chesnokova3
1Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia.
Background:
Prospective data on the value of oxidative stress in the pathogenesis of B-CLL are limited, and data on the relationship between oxidative stress and the presence of cytogenetic abnormalities (CA) in this pathology are almost absent. In the present study, we evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and antioxidant biomarkers [ceruloplasmin (CP) level and glutathione peroxidase (GPx) activity] in B-CLL and investigated the relationship between these biomarkers and the presence of CA.
Material And Methods:
A total of 64 B-CLL patients were grouped with respect to the Rai stages of the disease, then to the mutated/unmutated status of IGHV genes as well as to the presence/absence of CA. The type and frequency of CA in the B-CLL cells were determined by fluorescence in situ hybridization. Control group included 30 healthy volunteers. The CD, MDA, and nitrite levels as well as the GPx activity were evaluated spectrophotometrically; the CP level was evaluated turbidimetrically.
Results:
Compared to control, the B-CLL patients had increased CD, MDA, and nitrite levels as well as increased CP level and decreased GPx activity, which was observed at all Rai stages of the disease. CA were identified in 47 patients: del(13q14.3) as a single CA occurred in 18 patients, del(11q22.3) in 5 patients, del(17p13.1) in 4 patients, tri 12 in 5 patients, and multiple CA occurred in 15 patients. Compared to patients without CA, isolated del(17p13.1) was associated with higher CD and MDA levels while multiple CA with elevated CD levels only. The nitrite and CP levels and the activity of GPx in patients with CA were close to those in patients with normal FISH. The odds of harboring CA increased by a factor of 1.88 (p = 0.004) for every one unit increase in serum CD level (μmol/L), as assessed by binomial logistic regression.
Conclusion:
The results indicate that B-CLL patients experience increased oxidative stress and the relative deficiency of the antioxidant defense system. Increased CD level was independently associated with greater likelihood of harboring CA.
