Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload.

OBJECTIVE: To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). METHODS: We examined the levels of superoxide anion (O2-), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. RESULTS: Patients with IOL showed higher O2- levels (39.4 MFI) than normal controls (22.7 MFI, p=0.0356) and patients at diagnosis (19.4 MFI, p=0.0049). Antioxidant systems, except SOD activity, exhibited significant changes in IOL patients with respect to controls (CAT: 7.1 vs 2.7nmol/ml/min, p=0.0023; GPx: 50.9 vs 76.4nmol/ml/min, p=0.0291; GSH: 50.2 vs 24.1 MFI, p=0.0060). Furthermore, mitochondrial dysfunction was only detected in IOL cases compared to controls (ΔΨm: 3.6 vs 6.4 MFI, p=0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients. CONCLUSION: Oxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.

Increased oxidative damage associated with unfavorable cytogenetic subgroups in chronic lymphocytic leukemia.

Oxidative stress contributes to genomic instability in chronic lymphocytic leukemia (CLL), but its relationship with the acquisition of specific chromosomal abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8-oxo-2'-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels, and we compared them among the cytogenetic subgroups established using fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG and/or MDA were observed in patients with unfavorable cytogenetic aberrations (17p and 11q deletions) compared to the 13q deletion group. TP53 deletion patients exhibited a diminished DNA repair efficiency. Finally, cases with normal FISH also showed enhanced 8-oxo-dG, which could result in adverse outcomes.

Early ROS-mediated DNA damage and oxidative stress biomarkers in Monoclonal B Lymphocytosis.

Monoclonal B Lymphocytosis (MBL) is defined as asymptomatic monoclonal B-cell expansion characterised by a CLL-phenotype, but with less than 5×10(9)/l circulating cells. Reactive oxygen species (ROS)-mediated cell damage plays a critical role in the initiation of carcinogenesis as well as in malignant transformation. The goal of this study was to perform an analysis of the oxidative stress statuses of patients affected by MBL and chronic lymphocytic leukaemia (CLL). We examined peripheral blood and urine specimens from 29 patients with MBL, 55 with CLL and 31 healthy subjects. There was a significant increase in the occurrence of the mutagenic base 8-oxo-2'-deoxiguanosine (8-oxo-dG) in the lymphocytes and urine of MBL and CLL patients compared with controls. Significant differences were also observed in the levels of the lipid peroxidation product malondialdehyde (MDA) and in the oxidised/reduced glutathione (GSSG/GSH) ratio, although an increase in 8-isoprostane was not detected. Interestingly, the antioxidant catalase activity of circulating lymphocytes decreased in the patient groups. In conclusion, early oxidative stress exists in patients with MBL and CLL, causing damage to DNA and lipid structures. The higher levels of 8-oxo-dG in lymphocytes than in urine may be related to a decrease in the capacity of DNA repair systems. There were no differences in the oxidative statuses of the MBL and CLL patients, suggesting that oxidative injuries appear during a pre-leukaemic state of the disease.