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Głowacki S , Synowiec E , Szwed M , Toma M , Skorski T , Śliwiński T
Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells
Biomolecules. 2021 Apr 20;11(4)
PMID: 33924068 PMCID: PMC8074285 URL: https://www.ncbi.nlm.nih.gov/pubmed/33924068
AbstractChronic myeloid leukemia (CML) develops due to the presence of the BCR-ABL1 protein, a target of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), used in a CML therapy. CML eradication is a challenge due to developing resistance to TKIs. BCR-ABL1 induces endogenous oxidative stress leading to genomic instability and development of TKI resistance. Model CML cells susceptible or resistant to IM, as well as wild-type, non-cancer cells without the BCR-ABL1 protein were treated with IM, hydrogen peroxide (H(2)O(2)) as a model trigger of external oxidative stress, or with IM+H(2)O(2). Accumulation of reactive oxygen species (ROS), DNA damage, activity of selected antioxidant enzymes and glutathione (GSH), and mitochondrial potential (MMP) were assessed. We observed increase in ROS accumulation in BCR-ABL1 positive cells and distinct levels of ROS accumulation in IM-susceptible cells when compared to IM-resistant ones, as well as increased DNA damage caused by IM action in sensitive cells. Depletion of GSH levels and a decreased activity of glutathione peroxidase (GPx) in the presence of IM was higher in the cells susceptible to IM. IM-resistant cells showed an increase of catalase activity and a depletion of MMP. BCR-ABL1 kinase alters ROS metabolism, and IM resistance is accompanied by the changes in activity of GPx, catalase, and alterations in MMP.
Notes2218-273x Głowacki, Sylwester Synowiec, Ewelina Szwed, Marzena Orcid: 0000-0002-2102-3741 Toma, Monika Skorski, Tomasz Śliwiński, Tomasz Orcid: 0000-0001-8385-7744 DEC-2012/05/N/NZ3/01014/Narodowe Centrum Nauki/ Journal Article Biomolecules. 2021 Apr 20;11(4):610. doi: 10.3390/biom11040610.