Involvement of Oxidative Stress in the Relapse of Acute Myeloid Leukemia

• Published in: The Journal of biological chemistry 2010-05, Vol.285 (20), p.15010-15015
• Main Authors: Zhou, Fu-Ling, Zhang, Wang-Gang, Wei, Yong-Chang, Meng, Shan, Bai, Gai-Gai, Wang, Bai-Yan, Yang, Hui-Yun, Tian, Wei, Meng, Xin, Zhang, Hui, Chen, She-Ping
• Format: Article
• Language: English
• Subjects: Adenosine Deaminase - metabolism; Adolescent; Adult; Aged; Antioxidant; Base Sequence; Case-Control Studies; DNA Damage; DNA Primers; Female; Glutathione Peroxidase - metabolism; Humans; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - enzymology; Leukemia, Myeloid, Acute - metabolism; Male; Middle Aged; Molecular Bases of Disease; Monoamine Oxidase - metabolism; Oxidative Stress; Reactive Oxygen Species (ROS); Recurrence; Superoxide Dismutase - metabolism; Tumor; Xanthine Oxidase - metabolism; Young Adult
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.103713

The aims of the present study were to determine the level of oxidative stress and the salient factors leading to the relapse of acute myeloid leukemia (AML). Oxidative stress-related parameters and the expressions of specific genes were monitored in 102 cases of AML during a pretreatment period from a primary status to a relapse status. In addition, age-matched healthy subjects were classified as controls. The activities of adenosine deaminase and xanthine oxidase were higher in the relapse condition, whereas those of glutathione peroxidase, monoamine oxidase, and superoxide dismutase, and the total antioxidant capacity (T-AOC) were lower in the primary condition and in controls. Of particular note, levels of advanced oxidation protein products, malondialdehyde, and 8-hydroxydeoxyguanosine were also significantly higher in relapse patients. Furthermore, real-time PCR with SYBR Green revealed that the expression levels of human thioredoxin (TRX) and indoleamine 2,3-dioxygenase were increased in relapse patients. Pearson correlation analysis revealed that the T-AOC was positively correlated with GSH but negatively correlated with 8-OHdG, TRX, and indoleamine 2,3-dioxygenase. Linear regression showed that a low T-AOC and up-regulated TRX expression were the independent factors correlated with relapse. A strong association between oxidative stress and the incidence of disease relapse was observed, which has potential prognosis implications. These results indicate that oxidative stress is a crucial feature of AML and probably affects the development and relapse of AML.