2026-09-14T06:29:44Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1551762025-04-30T19:25:41Zcom_10366_3966com_10366_3947com_10366_3946com_10366_3823col_10366_3967

Romo González, Marta Moreno-Paz, Sara García Hernández, Violeta Sánchez-Guijo Martín, Fermín Hernández Hernández, Ángel Chronic myeloid leukemia (CML) Reactive oxygen species (ROS) BCR-ABL Xanthine oxidoreductase (XOR) Allopurinol Tyrosine kinase inhibitors (TKIs) Imatinib Nilotinib [EN]Chronic myeloid leukemia (CML) is characterized by the expression of the oncogenic kinase BCR-ABL. Although tyrosine kinase inhibitors (TKIs) against BCR-ABL represent the standard therapeutic option for CML, resistances to TKIs can be a serious problem. Thus, the search for novel therapeutic approaches is still needed. CML cells show an increased ROS production, which is required for maintaining the BCR-ABL signaling cascade active. In line with that, reducing ROS levels could be an interesting therapeutic strategy for the clinical management of resistant CML. To analyze the therapeutic potential of xanthine oxidoreductase (XOR) in CML, we tested the effect of XOR inhibitor allopurinol. Here, we show for the first time the therapeutic potential of allopurinol against BCR-ABL-positive CML cells. Allopurinol reduces the proliferation and clonogenic ability of the CML model cell lines K562 and KCL22. More importantly, the combination of allopurinol with imatinib or nilotinib reduced cell proliferation in a synergistic manner. Moreover, the co-treatment arms hampered cell clonogenic capacity and induced cell death more strongly than each single-agent arm. The reduction of intracellular ROS levels and the attenuation of the BCR-ABL signaling cascade may explain these effects. Finally, the self-renewal potential of primary bone marrow cells from CML patients was also severely reduced especially by the combination of allopurinol with TKIs. In summary, here we show that XOR inhibition is an interesting therapeutic option for CML, which can enhance the effectiveness of the TKIs currently used in clinics. 2024-02-01 2024-02-01 2020 info:eu-repo/semantics/article Romo-González, M., Moreno-Paz, S., García-Hernández, V., Sánchez-Guijo, F., & Hernández-Hernández, Á. (2020). Inhibition of xanthine oxidoreductase enhances the potential of tyrosine kinase inhibitors against chronic myeloid leukemia. Antioxidants, 9(1), 74. https://doi.org/10.3390/antiox9010074 http://hdl.handle.net/10366/155176 10.3390/ANTIOX9010074 2076-3921 eng https://doi.org/10.3390/antiox9010074 BFU2014-56490-R info:eu-repo/semantics/openAccess MDPI