Oxidative Stress and Chronic Myeloid Leukemia: A Balance between ROS-Mediated Pro- and Anti-Apoptotic Effects of Tyrosine Kinase Inhibitors

The balanced reciprocal translocation t (9; 22) (q34; q11) and the BCR-ABL fusion gene, which produce p210 bcr-abl protein production with high tyrosine kinase activity, are characteristics of chronic myeloid leukemia, a myeloproliferative neoplasm. This aberrant protein affects several signaling pa...

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Bibliographic Details
Published in:Antioxidants 2024-04, Vol.13 (4), p.461
Main Authors: Allegra, Alessandro, Mirabile, Giuseppe, Caserta, Santino, Stagno, Fabio, Russo, Sabina, Pioggia, Giovanni, Gangemi, Sebastiano
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
BCR-ABL protein
BCR-ABL1
Cancer
Care and treatment
Cell cycle
Cell death
Cell division
Cell proliferation
chemoresistance
Chronic myeloid leukemia
Cloning
Cytochrome
DNA damage
DNA repair
Drug therapy
Enzymes
Fusion protein
Gene fusion
Genes
GTP-binding protein
Kinases
Leukemia
Ligands
Lipids
Mitochondria
Mutation
Myeloid leukemia
Neutrophils
Nilotinib
Oxidation
Oxidative stress
Pathophysiology
Phenols
Physiology
Proteins
Reactive oxygen species
Signal transduction
Stem cells
Tyrosine
Tyrosine kinase inhibitors
Vincristine
Vitamin E
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Summary:The balanced reciprocal translocation t (9; 22) (q34; q11) and the BCR-ABL fusion gene, which produce p210 bcr-abl protein production with high tyrosine kinase activity, are characteristics of chronic myeloid leukemia, a myeloproliferative neoplasm. This aberrant protein affects several signaling pathways connected to both apoptosis and cell proliferation. It has been demonstrated that tyrosine kinase inhibitor treatment in chronic myeloid leukemia acts by inducing oxidative stress and, depending on its level, can activate signaling pathways responsible for either apoptosis or survival in leukemic cells. Additionally, oxidative stress and reactive oxygen species generation also mediate apoptosis through genomic activation. Furthermore, it was shown that oxidative stress has a role in both BCR-ABL-independent and BCR-ABL-dependent resistance pathways to tyrosine kinases, while patients with chronic myeloid leukemia were found to have a significantly reduced antioxidant level. The ideal environment for tyrosine kinase inhibitor therapy is produced by a favorable oxidative status. We discuss the latest studies that aim to manipulate the redox system to alter the apoptosis of cancerous cells.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox13040461