Leukemia and Oxidative Stress Markers1

Leukemia is a common type of cancer in Taiwan (8th among all cancers in adults) and is the number one cancer among children’s in Taiwan. The cause of leukemia is multifactorial including genetic factor, viral infection, chemical carcinogens and radiation. A preponderance of evidence has strongly suggests that oxidative stress/damage plays an important role in carcinogenesis including the pathogenesis of leukemia. On the other hand, increasing evidence has indicated that chemotherapeutic drugs can work via enhancing the production of reactive oxygen species (ROS) to kill leukemic cells whereas elevated antioxidant levels may increase drug resistance. How ROS, a double-edged sword, affect leukemic patients is rather uncertain. Hence, the major objective of this research plan is two folds. One is to investigate the redox status of leukemic patients and the other is to delineate how cellular redox status modulates the effect of anticancer drugs on leukemic cells in vitro. Parameters of redox status such as antioxidant levels and oxidative damage markers are well established in my laboratory (Exp. Biol. Med. 228, 413-423, 2003; Free Radic. Biol. Med. 36, 580-591, 2004; J. Agri. Food Chem. 54, 1638-1645, 2006; Free Radic. Res. 41, 571-579, 2007) and have been determined in patients with thalassemia (Br. J Haematol. 128, 119-127), Huntington’s disease (BBRC 359, 335-340, 2007), or cardiovascular diseases (manuscript in preparation, for details please see preliminary data). We plan to determine the redox status of leukemic patients at three major time points: prior to treatment (induction), during treatment, and after remission. We will also determine the redox status of leukemic patients upon relapse. To achieve the 1st aim, we have trained a Ph.D. student with a B.S. degree in Nurse and a M.S. degree in medical Biotechnology to be responsible to coordinate all clinical samples including the analysis of background information of all patients enrolled in our study. This coordinator will be one of the keys to the success of this research plan. Toward the 2nd aim, we will use RNAi technique to knockdown certain antioxidant genes such as glutathione peroxidase or superoxide dismutase in leukemic cell line and then to use proteomic and metabolomic techniques to delineate how these antioxidant enzyme-knockdown cells response to anticancer drugs comparing to control cells. By completing this research plan, it should help to elucidate how oxidative stress may affect the onset and treatment of leukemia. Moreover, such study may even suggest new markers to monitor the treatment of leukemia.

Project ID:PC9709-0940
External Project ID:NSC97-2320-B182-013-MY3