Abstract

Abstract 2924

Patients with Low-risk MDS have ineffective hematopoiesis, which results in refractory cytopenias requiring frequent blood transfusions for anemia treatment, nevertheless iron overload can occur even without transfusions. Recent research showed that reactive oxygen species were higher while reduced glutathione GSH was lower in RBC and platelets of MDS patients,when compared to normal individuals. The presence of highly reactive free radicals may play a role in the peroxidation of membrane lipids. Indirect evidence supports the role of oxidative DNA damage in the pathogenesis of MDS. Studies of the expression of antioxidant enzymes suggest that many CD34+ progenitors have inadequate oxidative stress defence. In this study we evaluated lipid peroxidation products measuring the thiobarbituric acid reactive substances (TBARS) in bone marrow plasma (BMp) and peripheral blood plasma (PBp) in low risk MDS patients.

Materials and Methods:

BMp and PBp for TBARS determination were obtained from 15 Low and Int-1 Risk MDS patients: 4 males, 11 females, mean age 65.5 years (range 50–83) at least 30 days from the last transfusion. Ferritin (FE), Transferrin (Tf), Tf Saturation (Tfs) were performed on the same day. As a control for TBARS determination we used (BMp) and (PBp) from 15 healthy bone marrow adult donors for transplant, age range 20– 55 years. Plasma levels of lipid peroxidation products were estimated according to the method of Ohkawa et al. as modified by Yagi. Lipid peroxides were expressed as nmol of malondialdehyde (MDA) per ml of plasma. Statistical analysis were performed using unpaired and paired Student's t-test and Pearson correlation was used to establish the relationship between variables (SAS V.9.2).

Results:

In MDS patients BMp and PBp TBARS levels were significantly increased: 10.59±0.84 and 5.25±0.55 respectively compared with controls: 4.49±0.47 and 1.89±0.26 (p<0.0001). Eighty-six percent of the patients (13/15) showed high serum FE concentration, mean 1341.3 ng/ml (range 631–3000ng/ml) We detected a positive and significant correlation between TBARS in PBp and BMp with FE levels (r=0.68, p=0.0049) and (r=0.54, p=0.0363) respectively. Additionally, both TBARS levels were highly correlated with the Tfs: r=0.81 (p=0.0025) and r=0.87 (p=0.0005) for BMp and PBp respectively. Also the patients showed high correlation between Tfs and FE (r=0.73, p=0.011).

When patients were grouped according to the amount of blood transfusions in greater or less than 20, FE levels were 1793.5±224 and 824±188 (p=0.0063), and Tfs were 72.3%±3 and 45%±8 (p=0.0036) respectively. However, in both groups TBARS in BMp and PBp did not show significant differences. TBARS levels showed no significant correlations with haemoglobin concentration nor platelet number.

Conclusions:

To date, the role of oxidative stress in MDS has not been fully elucidated. The current results show elevated levels of TBARS in BMp and PBp in patients with low risk MDS, as an evidence of increased oxidative stress, probably caused by the cellular alterations observed in MDS. We can speculate that iron overload may be a contributing factor, as we found a positive correlation between FE and Tfs with TBARS in both BMp and PBp in our patient population.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.