Abstract
Myelodysplastic syndrome (MDS) is characterized by refractory cytopenias due to ineffective hematopoiesis. Some patients with severe anemia require multiple blood transfusions and develop iron overload. Consequently, reactive oxygen species (ROS) are generated concomitant with a decrease in cellular antioxidants such as reduced gluthatione (GSH). The generated oxidative stress contributes to cell damage, apoptosis and ineffective hematopoiesis.
Using flow cytometry, we measured the oxidative state of RBC, platelets and PMN in 14 low-risk MDS patients and 25 normal donors. The results indicate that the majority of the patients had higher ROS in RBC (2.79-fold) and platelets (2.91-fold) and lower GSH in their RBC (3.4-fold) and platelets (2.1-fold) than normal (p<0.005). As for PMN, there were no significant differences in ROS, although GSH was significantly (p<0.1) lower in MDS compared with normal donors. The oxidative stress in MDS cells could be ameliorated by a short in vitro treatment with the iron-chelators deferrioxamine and deferiprone, or with the anti-oxidant N-acetylcysteine. These results suggest that the decrease in transfusion requirements with increase in platelet and PMN counts in MDS patients treated with deferrioxamine may be due to indirect antioxidant effect of the iron chelator and suggest that treatment with a combination of iron-chelators and anti-oxidants might be more effective.
ROS generation and GSH content in MDS blood cells
Effect of iron chelations and an antioxidant on the oxidative status of MDS cells
Disclosure: No relevant conflicts of interest to declare.
