PB1926 THE RELATIONSHIP BETWEEN OXIDATIVE STRESS LEVELS, BCR-ABL1 TRANSCRIPT VALUES AND TREATMENT WITH TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Abstract

Background: Chronic myeloid leukaemia (CML) is a chronic myeloproliferative neoplasm associated with a BCR-ABL1 gene sequence. Some studies have shown that oxidative stress is involved in CML pathogenesis, genomic instability, disease progression and resistance to tyrosine-kinase inhibitors (TKI). Aims: To evaluate reactive oxygen species (ROS) levels and the total antioxidant capacity (TAC) in patients with CML at diagnosis and after treatment with TKI. Methods: ROS and TAC were evaluated in a group of CML patients, diagnosed according to the ELN/WHO criteria, and in a control group of healthy volunteers. Patients were divided by age, sex and treatment. ROS were measured using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). TAC was evaluated using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). CML patients were initially prescribed cytoreductive treatment (hydroxyurea) and then first or second generation TKI. Informed consent was obtained from all recruited subjects and the study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova, Romania, approval no. 74/23.02.2017. Results: The study group involved 47 CML patients (mean age 59.89 ± 13.35 years, age range 22-87): 24 males (51.06%, mean age 59.00 ± 14.99 years, age range 22-87) and 23 females (48.94%, mean age 60.83 ± 11.32 years, age range 34-80). Oxidative stress levels were higher in patients with CML vs. controls (p = 0.006): the mean TAC value was lower and the mean ROS level was significantly higher in the CML group vs. controls (TAC: 0.28 mM vs. 0.35 mM; ROS: 10.42 FI vs. 10.07 FI, FI = fluorescence intensity). The mean TAC value was significantly lower for each treatment subgroup vs. controls, and in particular for imatinib and dasatinib subgroups, and the mean ROS value was significantly higher for each treatment subgroup vs. controls. Changes of redox status in CML patients during treatment were related to the BCR-ABL1 transcript value.Summary/Conclusion: In our study, CML patients had at diagnosis higher ROS levels and lower TAC values compared with healthy controls. We observed changes in the redox status of CML patients during treatment. Alterations in the redox status may contribute to genomic instability and disease progression and might also be involved in the development of treatment resistance.