Oxidative Stress in CML Stem and Progenitor Cells Correlates with Response to Imatinib

The BCR/ABL kinase alters the oxidative environment in chronic myelogenous leukemia (CML) cells, but the consequences of the increased reactive oxygen species (ROS) levels on signaling pathways remain unknown. Increased intracellular peroxides in progenitors cells have been linked to DNA damage, and promote self-mutation which subsequently render imatinib to resistance and failure to eliminate all leukemia cells.

A total of 8 patients and 3 health controls were included in this study. 1 patient only at diagnosis, 3 patients at diagnosis and 3 months after treatment with Imatinib, 1 case after 3 and 6 month with Imatinib, 2 cases are long follow-up resistant patients and 1 with long follow-up and good response. Oxidative stress biomarkers were studied by flow cytometry in the bone marrow progenitor cells.

Not only levels of BCR-ABR and the number of CML stem cells were lower with the treatment, the oxidative stress biomarkers were lower too in normal controls and in CML cells in patients with response to imatinib but in the resistant ones oxidative stress biomarkers were higher in all stem and progenitor cells.

The levels of oxidative stress are significantly higher in CML cells than in healthy subjects and correlate with tumor burden as well as the response to imatinib. This data demonstrate a role of oxidative stress in restore normal hematopoiesis in CML patients and probably in imatinib resistance.

García:Celgene: Research Funding.