Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia
Joanna Antoszewska-Smith, Elzbieta Pawlowska and Janusz Blasiak
Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis. Introducing imatinib and other tyrosine kinase inhibitors (TKIs) to CML therapy radically improved its outcome, but TKIs-resistance became an emerging problem. TKI resistance can be associated with even higher ROS production than in TKI-sensitive cells. Therefore, ROS-induced self-mutagenesis of BCR-ABL1 can be crucial for CML progression and TKI resistance and in this way should be taken into account in therapeutic strategies. As a continuous production of ROS by BCR-ABL1 would lead to its self-destruction and death of CML cells, there must be mechanisms controlling this phenomenon. These can be dependent on DNA repair, which is modulated by BCR-ABL1 and can be different in CML stem and progenitor cells. Altogether, the mechanisms of the involvement of BCR-ABL1 in ROS signaling can be engaged in CML progression and TKI-resistance and warrant further study.
Acta Biochimica Polonica, 64(1), 1-10, Review, DOI: 10.18388/abp.2016_1396
Acta Biochimica Polonica is indexed in: Current Contents, Biochem. and Biophys. Citation Index, BIOSIS, Chemical Abstracts, Excerpta Medica, Medline, Index Copernicus, CBR
Acta Biochimica Polonica is a member of the Committee on Publication Ethics (COPE)
Copyright © by Pawel Pomorski and Polish Biochemical Society 2015