FREE RADICALS AND ELEMENTAL/CO-FACTORS EFFECT ON ROS SCAVANGING ENZYMES IN AML

Abstract

Acute myeloid leukemia (AML) is a malignant tumor of hematopoietic precursor cells of myeloid lineage that arise in bone marrow. It is a type of leukemia that is more common in adults. Although many therapeutic choices are available for AML cure but still this field needs to explore. This study is also continuation of exploring novel therapeutic targets which can be used for development of novel therapeutic interventions. In this study, an experimental model was also designed for AML. In the recent study, we measured the ROS level in the serum of 40 AML patients and 40 control subjects. The means of ROS in AML and healthy persons were 0.33±0.16 and 0.23±0.13 respectively. A significant difference was observed between AML patients and control (0.0045). Similarly, a significant increased ROS level (p = 0.0045) was found in AML induced rats as compared to healthy ones. Different parameters including age, gender, platelets, hemoglobin and smoking of diseased and control subjects were compared. A significant difference was seen in case of platelets, hemoglobin and smoking. Smoking has a direct correlation with ROS in AML patients (p=0.026). Increase in calcium concentration in AML patients, as observed in this study reveals that by regulating NOX5, calcium increase ROS production in bone marrow malignant cells. This ROS production is responsible for proliferation of leukemic cells and hindering of normal cells proliferation. In this study, phosphorylated ARC expression was also observed in AML patient as well as AML induced rats samples. ARC, which is an anti- apoptotic protein, is responsible for reduction of apoptosis by inhibiting caspase-8. ARC over expression also inhibits potassium channels which in turn increase potassium concentration intracellularly. Increase potassium concentration results in inhibition of apoptotic cell shrinkage. ARC is also a calcium binding protein. When ARC and calcium binds with each other, all calcium dependent apoptotic processes are inhibited. All these pathways, which are discussed above, ultimately lead to anti-apoptotic effect in AML patients which is the main characteristic of the disease. In the future, further studies are required to correlate ARC, calcium, potassium and ROS. By establishing this correlation, we can get novel therapeutic targets in AML patients, which are required to inhibit by new therapeutic interventions.