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Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies

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Abstract

The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. Mitochondria are the key organelles for the maintenance of myocardial tissue homeostasis. However, cardiotoxicity associated with BCR-ABL1 TKIs can directly or indirectly cause mitochondrial damage and dysfunction, playing a pivotal role in cardiomyocytes homeostatic system and putting the cancer survivors at higher risk. In this review, we summarize the cardiotoxicity caused by BCR-ABL1 TKIs and the underlying mechanisms, which contribute dominantly to the damage of mitochondrial structure and dysfunction: endoplasmic reticulum (ER) stress, mitochondrial stress, damage of myocardial cell mitochondrial respiratory chain, increased production of mitochondrial reactive oxygen species (ROS), and other kinases and other potential mechanisms of cardiotoxicity induced by BCR-ABL1 TKIs. Furthermore, detection and management of BCR-ABL1 TKIs will promote our rational use, and cardioprotection strategies based on mitochondria will improve our understanding of the cardiotoxicity from a mitochondrial perspective. Ultimately, we hope shed light on clinical decision-making. By integrate and learn from both research and practice, we will endeavor to minimize the mitochondria-mediated cardiotoxicity and reduce the adverse sequelae associated with BCR-ABL1 TKIs.

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Data availability is not applicable to this review as no new data were created in this study.

References

  1. Jabbour, E., & Kantarjian, H. (2020). Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. American Journal of Hematology, 95(6), 691–709. https://doi.org/10.1002/ajh.25792

    Article  CAS  PubMed  Google Scholar 

  2. Faderl, S., Talpaz, M., Estrov, Z., O’Brien, S., Kurzrock, R., & Kantarjian, H. M. (1999). The biology of chronic myeloid Leukemia. The New England Journal of Medicine, 341(3), 164–172. https://doi.org/10.1056/nejm199907153410306

    Article  CAS  PubMed  Google Scholar 

  3. Iacoboni, S. J., Plunkett, W., Kantarjian, H. M., Estey, E., Keating, M. J., McCredie, K. B., & Freireich, E. J. (1986). High-dose cytosine arabinoside: Treatment and cellular pharmacology of chronic myelogenous Leukemia blast crisis. Journal of clinical oncology : Official journal of the American Society of Clinical Oncology, 4(7), 1079–1088. https://doi.org/10.1200/jco.1986.4.7.1079

    Article  CAS  PubMed  Google Scholar 

  4. Esteban-Villarrubia, J., Soto-Castillo, J. J., Pozas, J., San Roman-Gil, M., Orejana-Martin, I., Torres-Jimenez, J., Carrato, A., Alonso-Gordoa, T., & Molina-Cerrillo, J. (2020). Tyrosine kinase receptors in oncology. International Journal of Molecular Sciences, 21(22), 48. https://doi.org/10.3390/ijms21228529

    Article  CAS  Google Scholar 

  5. Braun, T. P., Eide, C. A., & Druker, B. J. (2020). Response and Resistance to BCR-ABL1-Targeted Therapies. Cancer cell, 37(4), 530–542. https://doi.org/10.1016/j.ccell.2020.03.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hehlmann, R., Müller, M. C., Lauseker, M., Hanfstein, B., Fabarius, A., Schreiber, A., Proetel, U., Pletsch, N., Pfirrmann, M., Haferlach, C., Schnittger, S., Einsele, H., Dengler, J., Falge, C., Kanz, L., Neubauer, A., Kneba, M., Stegelmann, F., Pfreundschuh, M., … Hochhaus, A. (2014). Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: Results from the randomized CML-study IV. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 32(5), 415–423. https://doi.org/10.1200/jco.2013.49.9020

    Article  PubMed  Google Scholar 

  7. Cortes, J. E., Saglio, G., Kantarjian, H. M., Baccarani, M., Mayer, J., Boqué, C., Shah, N. P., Chuah, C., Casanova, L., Bradley-Garelik, B., Manos, G., & Hochhaus, A. (2016). Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 34(20), 2333–2340. https://doi.org/10.1200/JCO.2015.64.8899

    Article  CAS  PubMed  Google Scholar 

  8. Bhamidipati, P. K., Kantarjian, H., Cortes, J., Cornelison, A. M., & Jabbour, E. (2013). Management of imatinib-resistant patients with chronic myeloid leukemia. Therapeutic Advances in Hematology, 4(2), 103–117. https://doi.org/10.1177/2040620712468289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kamath, A. V., Wang, J., Lee, F. Y., & Marathe, P. H. (2008). Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): A potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemotherapy and Pharmacology, 61(3), 365–376.

    Article  CAS  PubMed  Google Scholar 

  10. Reinwald, M., Schleyer, E., Kiewe, P., Blau, I. W., Burmeister, T., Pursche, S., Neumann, M., Notter, M., Thiel, E., Hofmann, W.-K., Kolb, H.-J., Burdach, S., & Bender, H.-U. (2014). Efficacy and pharmacologic data of second-generation tyrosine kinase inhibitor nilotinib in BCR-ABL-positive Leukemia patients with central nervous system relapse after allogeneic stem cell transplantation. BioMed Research International. https://doi.org/10.1155/2014/637059

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hoy, S. M. (2014). Ponatinib: A review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic Leukaemia. Drugs, 74(7), 793–806. https://doi.org/10.1007/s40265-014-0216-6

    Article  CAS  PubMed  Google Scholar 

  12. Gunnarsson, N., Sandin, F., Höglund, M., Stenke, L., Björkholm, M., Lambe, M., Olsson-Strömberg, U., Richter, J., & Själander, A. (2016). Population-based assessment of chronic myeloid leukemia in Sweden: Striking increase in survival and prevalence. European Journal of Haematology, 97(4), 387–392. https://doi.org/10.1111/ejh.12743

    Article  CAS  PubMed  Google Scholar 

  13. Saussele, S., Krauss, M. P., Hehlmann, R., Lauseker, M., Proetel, U., Kalmanti, L., Hanfstein, B., Fabarius, A., Kraemer, D., Berdel, W. E., Bentz, M., Staib, P., de Wit, M., Wernli, M., Zettl, F., Hebart, H. F., Hahn, M., Heymanns, J., Schmidt-Wolf, I., … Müller, M. C. (2015). Impact of comorbidities on overall survival in patients with chronic myeloid Leukemia: Results of the randomized CML study IV. Blood, 126(1), 42–49. https://doi.org/10.1182/blood-2015-01-617993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sanz, A., Ayala, R., Hernández, G., Lopez, N., Gil-Alos, D., Gil, R., Colmenares, R., Carreño-Tarragona, G., Sánchez-Pina, J., Alonso, R. A., García-Barrio, N., Pérez-Rey, D., Meloni, L., Calbacho, M., Cruz-Rojo, J., Pedrera-Jiménez, M., Serrano-Balazote, P., de la Cruz, J., & Martínez-López, J. (2022). Outcomes and patterns of treatment in chronic myeloid leukemia, a global perspective based on a real-world data global network. Blood Cancer Journal, 12(6), 94. https://doi.org/10.1038/s41408-022-00692-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tajiri, K., Aonuma, K., & Sekine, I. (2017). Cardiovascular toxic effects of targeted cancer therapy. Japanese Journal of Clinical Oncology, 47(9), 779–785. https://doi.org/10.1093/jjco/hyx071

    Article  PubMed  Google Scholar 

  16. Moslehi, J. J., & Deininger, M. (2015). Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid Leukemia. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 33(35), 4210–4218. https://doi.org/10.1200/jco.2015.62.4718

    Article  CAS  PubMed  Google Scholar 

  17. Wells, Q. S., & Lenihan, D. J. (2010). Reversibility of left ventricular dysfunction resulting from chemotherapy: Can this be expected? Progress in Cardiovascular Diseases, 53(2), 140–148. https://doi.org/10.1016/j.pcad.2010.06.005

    Article  PubMed  Google Scholar 

  18. Maharsy, W., Aries, A., Mansour, O., Komati, H., & Nemer, M. (2014). Ageing is a risk factor in imatinib mesylate cardiotoxicity. European Journal of Heart Failure, 16(4), 367–376. https://doi.org/10.1002/ejhf.58

    Article  CAS  PubMed  Google Scholar 

  19. Gugliotta, G., Castagnetti, F., Breccia, M., Levato, L., D’Adda, M., Stagno, F., Tiribelli, M., Salvucci, M., Fava, C., Martino, B., Cedrone, M., Bocchia, M., Trabacchi, E., Cavazzini, F., Usala, E., Russo Rossi, A., Bochicchio, M. T., Soverini, S., Alimena, G., … Rosti, G. (2015). Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia. Haematologica, 100(9), 1146–1150. https://doi.org/10.3324/haematol.2015.129221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ran, H. H., Zhang, R., Lu, X. C., Yang, B., Fan, H., & Zhu, H. L. (2012). Imatinib-induced decompensated heart failure in an elderly patient with chronic myeloid leukemia: Case report and literature review. Journal of Geriatric Cardiology: JGC, 9(4), 411–414. https://doi.org/10.3724/sp.J.1263.2012.05251

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hoffmann, V. S., Baccarani, M., Hasford, J., Castagnetti, F., Di Raimondo, F., Casado, L. F., Turkina, A., Zackova, D., Ossenkoppele, G., Zaritskey, A., Höglund, M., Simonsson, B., Indrak, K., Sninska, Z., Sacha, T., Clark, R., Bogdanovic, A., Hellmann, A., Griskevicius, L., … Hehlmann, R. (2017). Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia, 31(3), 593–601. https://doi.org/10.1038/leu.2016.246

    Article  CAS  PubMed  Google Scholar 

  22. Berman, E. (2022). How I treat chronic-phase chronic myelogenous Leukemia. Blood, 139(21), 3138–3147. https://doi.org/10.1182/blood.2021011722

    Article  CAS  PubMed  Google Scholar 

  23. Gustafson, D., Fish, J. E., Lipton, J. H., & Aghel, N. (2020). Mechanisms of cardiovascular toxicity of BCR-ABL1 Tyrosine kinase inhibitors in chronic myelogenous Leukemia. Current Hematologic Malignancy Reports, 15(1), 20–30. https://doi.org/10.1007/s11899-020-00560-x

    Article  PubMed  Google Scholar 

  24. Osellame, L. D., Blacker, T. S., & Duchen, M. R. (2012). Cellular and molecular mechanisms of mitochondrial function. Best Practice & Research Clinical endocrinology & metabolism, 26(6), 711–723. https://doi.org/10.1016/j.beem.2012.05.003

    Article  CAS  Google Scholar 

  25. Kerkelä, R., Grazette, L., Yacobi, R., Iliescu, C., Patten, R., Beahm, C., Walters, B., Shevtsov, S., Pesant, S., Clubb, F. J., Rosenzweig, A., Salomon, R. N., Van Etten, R. A., Alroy, J., Durand, J. B., & Force, T. (2006). Cardiotoxicity of the Cancer Therapeutic Agent Imatinib Mesylate. Nature medicine, 12(8), 908–916. https://doi.org/10.1038/nm1446

    Article  CAS  PubMed  Google Scholar 

  26. Will, Y., Dykens, J. A., Nadanaciva, S., Hirakawa, B., Jamieson, J., Marroquin, L. D., Hynes, J., Patyna, S., & Jessen, B. A. (2008). Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells. Toxicological Sciences : An Official Journal of the Society of Toxicology, 106(1), 153–161. https://doi.org/10.1093/toxsci/kfn157

    Article  CAS  PubMed  Google Scholar 

  27. Varga, Z. V., Ferdinandy, P., Liaudet, L., & Pacher, P. (2015). Drug-induced mitochondrial dysfunction and cardiotoxicity. American Journal of Physiology Heart and Circulatory Physiology, 309(9), H1453-1467. https://doi.org/10.1152/ajpheart.00554.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Murphy, E., Ardehali, H., Balaban, R. S., DiLisa, F., Dorn, G. W., 2nd., Kitsis, R. N., Otsu, K., Ping, P., Rizzuto, R., Sack, M. N., Wallace, D., & Youle, R. J. (2016). Mitochondrial function, biology, and role in disease: A scientific statement from the american heart association. Circulation Research, 118(12), 1960–1991. https://doi.org/10.1161/res.0000000000000104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nunnari, J., & Suomalainen, A. (2012). Mitochondria: In sickness and in health. Cell, 148(6), 1145–1159. https://doi.org/10.1016/j.cell.2012.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shadel, G. S., & Horvath, T. L. (2015). Mitochondrial ROS signaling in organismal homeostasis. Cell, 163(3), 560–569. https://doi.org/10.1016/j.cell.2015.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nguyen, B. Y., Ruiz-Velasco, A., Bui, T., Collins, L., Wang, X., & Liu, W. (2019). Mitochondrial function in the heart: The insight into mechanisms and therapeutic potentials. British Journal of Pharmacology, 176(22), 4302–4318. https://doi.org/10.1111/bph.14431

    Article  CAS  PubMed  Google Scholar 

  32. Pouwer, M. G., Pieterman, E. J., Verschuren, L., Caspers, M. P. M., Kluft, C., Garcia, R. A., Aman, J., Jukema, J. W., & Princen, H. M. G. (2018). The BCR-ABL1 inhibitors imatinib and ponatinib decrease plasma cholesterol and atherosclerosis, and nilotinib and ponatinib activate coagulation in a translational mouse model. Frontiers in Cardiovascular Medicine. https://doi.org/10.3389/fcvm.2018.00055

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tang, X., Wang, Z., Hu, S., & Zhou, B. (2022). Assessing Drug-induced mitochondrial toxicity in cardiomyocytes: Implications for preclinical cardiac safety evaluation. Pharmaceutics. https://doi.org/10.3390/pharmaceutics14071313

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang, W., Fernandez-Sanz, C., & Sheu, S. S. (2018). Regulation of mitochondrial bioenergetics by the non-canonical roles of mitochondrial dynamics proteins in the heart. Biochimica et Biophysica Acta Molecular Basis of Disease, 1864(5 Pt B), 1991–2001. https://doi.org/10.1016/j.bbadis.2017.09.004

    Article  CAS  PubMed  Google Scholar 

  35. Shoshan-Barmatz, V., De Pinto, V., Zweckstetter, M., Raviv, Z., Keinan, N., & Arbel, N. (2010). VDAC, a multi-functional mitochondrial protein regulating cell life and death. Molecular Aspects of Medicine, 31(3), 227–285. https://doi.org/10.1016/j.mam.2010.03.002

    Article  CAS  PubMed  Google Scholar 

  36. Vercellino, I., & Sazanov, L. A. (2022). The assembly, regulation and function of the mitochondrial respiratory chain. Nature Reviews Molecular Cell Biology, 23(2), 141–161. https://doi.org/10.1038/s41580-021-00415-0

    Article  CAS  PubMed  Google Scholar 

  37. Vogel, F., Bornhövd, C., Neupert, W., & Reichert, A. S. (2006). Dynamic subcompartmentalization of the mitochondrial inner membrane. The Journal of cell biology, 175(2), 237–247. https://doi.org/10.1083/jcb.200605138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cao, Y. P., & Zheng, M. (2019). Mitochondrial dynamics and inter-mitochondrial communication in the heart. Archives of Biochemistry and Biophysics. https://doi.org/10.1016/j.abb.2019.01.017

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yin, Y., & Shen, H. (2021). Advances in cardiotoxicity induced by altered mitochondrial dynamics and mitophagy. Frontiers in Cardiovascular Medicine, 8, 739095. https://doi.org/10.3389/fcvm.2021.739095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sack, M. N., Fyhrquist, F. Y., Saijonmaa, O. J., Fuster, V., & Kovacic, J. C. (2017). Basic biology of oxidative stress and the cardiovascular system: Part 1 of a 3-Part Series. Journal of the American College of Cardiology, 70(2), 196–211. https://doi.org/10.1016/j.jacc.2017.05.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lauritzen, K. H., Kleppa, L., Aronsen, J. M., Eide, L., Carlsen, H., Haugen, Ø. P., Sjaastad, I., Klungland, A., Rasmussen, L. J., Attramadal, H., Storm-Mathisen, J., & Bergersen, L. H. (2015). Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure. American journal of physiology Heart and circulatory physiology, 309(3), 434–449. https://doi.org/10.1152/ajpheart.00253.2014

    Article  CAS  Google Scholar 

  42. Liu, M., & Wu, Y. (2022). Role of mitophagy in coronary heart Disease: Targeting the mitochondrial dysfunction and inflammatory regulation. Frontiers in Cardiovascular Medicine, 9, 819454. https://doi.org/10.3389/fcvm.2022.819454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhou, B., & Tian, R. (2018). Mitochondrial dysfunction in pathophysiology of heart failure. The Journal of clinical Investigation, 128(9), 3716–3726. https://doi.org/10.1172/jci120849

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zamorano, J. L., Lancellotti, P., Rodriguez Muñoz, D., Aboyans, V., Asteggiano, R., Galderisi, M., Habib, G., Lenihan, D. J., Lip, G. Y., Lyon, A. R., Lopez Fernandez, T., Mohty, D., Piepoli, M. F., Tamargo, J., Torbicki, A., Suter, T. M., Zamorano, J. L., Aboyans, V., Achenbach, S., … Windecker, S. (2017). 2016 ESC Position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines: The task force for cancer treatments and cardiovascular toxicity of the european society of cardiology (ESC). European Journal of Heart Failure, 19(1), 9–42. https://doi.org/10.1002/ejhf.654

    Article  PubMed  Google Scholar 

  45. Force, T., Krause, D. S., & Van Etten, R. A. (2007). Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nature Reviews Cancer, 7(5), 332–344. https://doi.org/10.1038/nrc2106

    Article  CAS  PubMed  Google Scholar 

  46. Liu, Y., Huang, Y., Xu, C., An, P., Luo, Y., Jiao, L., Luo, J., & Li, Y. (2022). Mitochondrial dysfunction and therapeutic perspectives in cardiovascular diseases. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms232416053

    Article  PubMed  PubMed Central  Google Scholar 

  47. Waseem, M., & Parvez, S. (2013). Mitochondrial dysfunction mediated cisplatin induced toxicity: Modulatory role of curcumin. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 53, 334–342. https://doi.org/10.1016/j.fct.2012.11.055

    Article  CAS  PubMed  Google Scholar 

  48. Gorini, S., De Angelis, A., Berrino, L., Malara, N., Rosano, G., & Ferraro, E. (2018). Chemotherapeutic drugs and mitochondrial dysfunction: Focus on doxorubicin, trastuzumab, and sunitinib. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2018/7582730

    Article  PubMed  PubMed Central  Google Scholar 

  49. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004). Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews, 56(2), 185–229. https://doi.org/10.1124/pr.56.2.6

    Article  CAS  PubMed  Google Scholar 

  50. Wu, D., Wang, X., & Sun, H. (2018). The role of mitochondria in cellular toxicity as a potential drug target. Cell Biology and Toxicology, 34(2), 87–91. https://doi.org/10.1007/s10565-018-9425-1

    Article  CAS  PubMed  Google Scholar 

  51. Kim, C. W., & Choi, K. C. (2021). Effects of anticancer drugs on the cardiac mitochondrial toxicity and their underlying mechanisms for novel cardiac protective strategies. Life Sciences, 277, 119607. https://doi.org/10.1016/j.lfs.2021.119607

    Article  CAS  PubMed  Google Scholar 

  52. Lushchak, V. I. (2014). Free radicals, reactive oxygen species, oxidative stress and its classification. Chemico-Biological Interactions, 224, 164–175. https://doi.org/10.1016/j.cbi.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  53. Holmström, K. M., & Finkel, T. (2014). Cellular mechanisms and physiological consequences of redox-dependent signalling. Nature Reviews Molecular cell biology, 15(6), 411–421. https://doi.org/10.1038/nrm3801

    Article  CAS  PubMed  Google Scholar 

  54. Fu, Z., Guo, J., Jing, L., Li, R., Zhang, T., & Peng, S. (2010). Enhanced toxicity and ROS generation by doxorubicin in primary cultures of cardiomyocytes from neonatal metallothionein-I/II null mice. Toxicology in vitro : An International Journal Published in Association with BIBRA, 24(6), 1584–1591. https://doi.org/10.1016/j.tiv.2010.06.009

    Article  CAS  PubMed  Google Scholar 

  55. Tocchetti, C. G., Molinaro, M., Angelone, T., Lionetti, V., Madonna, R., Mangiacapra, F., Moccia, F., Penna, C., Sartiani, L., Quaini, F., & Pagliaro, P. (2015). Nitroso-redox balance and modulation of basal myocardial function: An update from the italian society of cardiovascular research (SIRC). Current Drug Targets, 16(8), 895–903. https://doi.org/10.2174/1389450116666150304103517

    Article  CAS  PubMed  Google Scholar 

  56. Patergnani, S., Suski, J. M., Agnoletto, C., Bononi, A., Bonora, M., De Marchi, E., Giorgi, C., Marchi, S., Missiroli, S., Poletti, F., Rimessi, A., Duszynski, J., Wieckowski, M. R., & Pinton, P. (2011). Calcium signaling around mitochondria associated membranes (MAMs). Cell Communication and Signaling : CCS,919. https://doi.org/10.1186/1478-811x-9-19

    Article  Google Scholar 

  57. Olson, M. L., Chalmers, S., & McCarron, J. G. (2012). Mitochondrial organization and Ca2+ uptake. Biochemical Society Transactions, 40(1), 158–167. https://doi.org/10.1042/bst20110705

    Article  CAS  PubMed  Google Scholar 

  58. Zhang, Z., Zhao, L., Zhou, Y., Lu, X., Wang, Z., Wang, J., & Li, W. (2017). Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress. Apoptosis : An International Journal on Programmed Cell Death, 22(5), 647–661. https://doi.org/10.1007/s10495-017-1351-9

    Article  CAS  PubMed  Google Scholar 

  59. Marcolino, M. S., Boersma, E., Clementino, N. C., Nunes, M. D., Barbosa, M. M., Silva, M. H., Geleijnse, M. L., & Ribeiro, A. L. (2011). The duration of the use of imatinib mesylate is only weakly related to elevated BNP levels in chronic myeloid Leukaemia patients. Hematological Oncology, 29(3), 124–130. https://doi.org/10.1002/hon.967

    Article  CAS  PubMed  Google Scholar 

  60. Turrisi, G., Montagnani, F., Grotti, S., Marinozzi, C., Bolognese, L., & Fiorentini, G. (2010). Congestive heart failure during imatinib mesylate treatment. International Journal of Cardiology, 145(1), 148–150. https://doi.org/10.1016/j.ijcard.2009.07.006

    Article  PubMed  Google Scholar 

  61. Rousselot, P., Cony-Makhoul, P., Nicolini, F., Mahon, F. X., Berthou, C., Réa, D., Reiffers, J., Bornand, A., Saint-Jean, O., Guilhot, J., & Guilhot, F. (2013). Long-term safety and efficacy of imatinib mesylate (Gleevec®) in elderly patients with chronic phase chronic myelogenous leukemia: Results of the AFR04 study. American Journal of Hematology, 88(1), 1–4. https://doi.org/10.1002/ajh.23330

    Article  CAS  PubMed  Google Scholar 

  62. Toubert, M. E., Vercellino, L., Faugeron, I., Lussato, D., Hindie, E., & Bousquet, G. (2011). Fatal heart failure after a 26-month combination of tyrosine kinase inhibitors in a papillary thyroid cancer. Thyroid: Official Journal of the American Thyroid Association, 21(4), 451–454. https://doi.org/10.1089/thy.2010.0270

    Article  CAS  PubMed  Google Scholar 

  63. Bouitbir, J., Panajatovic, M. V., Frechard, T., Roos, N. J., & Krähenbühl, S. (2020). Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells. Front Pharmacol, 11, 1106. https://doi.org/10.3389/fphar.2020.01106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bouitbir, J., Panajatovic, M. V., & Krähenbühl, S. (2022). Mitochondrial Toxicity Associated with Imatinib and Sorafenib in Isolated Rat Heart Fibers and the Cardiomyoblast H9c2 Cell Line. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms23042282

    Article  PubMed  PubMed Central  Google Scholar 

  65. Slee, E. A., Adrain, C., & Martin, S. J. (2001). Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. The Journal of Biological Chemistry, 276(10), 7320–7326. https://doi.org/10.1074/jbc.M008363200

    Article  CAS  PubMed  Google Scholar 

  66. Joza, N., Susin, S. A., Daugas, E., Stanford, W. L., Cho, S. K., Li, C. Y., Sasaki, T., Elia, A. J., Cheng, H. Y., Ravagnan, L., Ferri, K. F., Zamzami, N., Wakeham, A., Hakem, R., Yoshida, H., Kong, Y. Y., Mak, T. W., Zúñiga-Pflücker, J. C., Kroemer, G., & Penninger, J. M. (2001). Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature, 410(6828), 549–554. https://doi.org/10.1038/35069004

    Article  CAS  PubMed  Google Scholar 

  67. Finsterer, J., & Ohnsorge, P. (2013). Influence of mitochondrion-toxic agents on the cardiovascular system. Regulatory Toxicology and Pharmacology: RTP, 67(3), 434–445. https://doi.org/10.1016/j.yrtph.2013.09.002

    Article  CAS  PubMed  Google Scholar 

  68. Yu, C., Krystal, G., Varticovksi, L., McKinstry, R., Rahmani, M., Dent, P., & Grant, S. (2002). Pharmacologic mitogen-activated protein/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase inhibitors interact synergistically with STI571 to induce apoptosis in Bcr/Abl-expressing human Leukemia cells. Cancer Research, 62(1), 188–199.

    CAS  PubMed  Google Scholar 

  69. Thomson, M. (2002). Evidence of undiscovered cell regulatory mechanisms: Phosphoproteins and protein kinases in mitochondria. Cellular and Molecular Life Sciences : CMLS, 59(2), 213–219. https://doi.org/10.1007/s00018-002-8417-7

    Article  CAS  PubMed  Google Scholar 

  70. McMullen, C. J., Chalmers, S., Wood, R., Cunningham, M. R., & Currie, S. (2020). Sunitinib and Imatinib display differential cardiotoxicity in adult rat cardiac fibroblasts that involves a role for calcium/calmodulin dependent protein kinase II. Frontiers in Cardiovascular Medicine, 7, 630480. https://doi.org/10.3389/fcvm.2020.630480

    Article  CAS  PubMed  Google Scholar 

  71. Song, C., Li, D., Zhang, J., & Zhao, X. (2022). Role of ferroptosis in promoting cardiotoxicity induced by Imatinib Mesylate via down-regulating Nrf2 pathways in vitro and in vivo. Toxicology and Applied Pharmacology, 435, 115852. https://doi.org/10.1016/j.taap.2021.115852

    Article  CAS  PubMed  Google Scholar 

  72. Singh, A. P., Umbarkar, P., Tousif, S., & Lal, H. (2020). Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib. International Journal of Cardiology, 316, 214–221. https://doi.org/10.1016/j.ijcard.2020.05.077

    Article  PubMed  Google Scholar 

  73. Makeeva, L. M., Emelina, E. I., Gendlin, G. E., Nikitin, I. G., Vasyuk, Y. A., & Nesvetov, V. V. (2017). Pulmonary arterial hypertension and chronic heart failure as dasatinib cardiotoxicity. A case report. Kardiologiia, 57(S4), 53–60.

    Article  CAS  PubMed  Google Scholar 

  74. Motokawa, T., Ikeda, S., Ueno, Y., Eguchi, M., Minami, T., Kawano, H., Kobayashi, K., Imaizumi, Y., & Maemura, K. (2022). Comparison of dasatinib- and imatinib-related cardiotoxic adverse events in Japanese patients with chronic myeloid Leukemia and gastrointestinal stromal tumor. Circulation Reports, 4(1), 1–8. https://doi.org/10.1253/circrep.CR-21-0140

    Article  PubMed  Google Scholar 

  75. Guignabert, C., Phan, C., Seferian, A., Huertas, A., Tu, L., Thuillet, R., Sattler, C., Le Hiress, M., Tamura, Y., Jutant, E. M., Chaumais, M. C., Bouchet, S., Manéglier, B., Molimard, M., Rousselot, P., Sitbon, O., Simonneau, G., Montani, D., & Humbert, M. (2016). Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension. The Journal of Clinical Investigation, 126(9), 3207–3218. https://doi.org/10.1172/jci86249

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kantarjian, H. M., Hughes, T. P., Larson, R. A., Kim, D. W., Issaragrisil, S., le Coutre, P., Etienne, G., Boquimpani, C., Pasquini, R., Clark, R. E., Dubruille, V., Flinn, I. W., Kyrcz-Krzemien, S., Medras, E., Zanichelli, M., Bendit, I., Cacciatore, S., Titorenko, K., Aimone, P., … Hochhaus, A. (2021). Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia, 35(2), 440–453. https://doi.org/10.1038/s41375-020-01111-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Aichberger, K. J., Herndlhofer, S., Schernthaner, G. H., Schillinger, M., Mitterbauer-Hohendanner, G., Sillaber, C., & Valent, P. (2011). Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. American Journal of Hematology, 86(7), 533–539. https://doi.org/10.1002/ajh.22037

    Article  CAS  PubMed  Google Scholar 

  78. Hadzijusufovic, E., Albrecht-Schgoer, K., Huber, K., Hoermann, G., Grebien, F., Eisenwort, G., Schgoer, W., Herndlhofer, S., Kaun, C., Theurl, M., Sperr, W. R., Rix, U., Sadovnik, I., Jilma, B., Schernthaner, G. H., Wojta, J., Wolf, D., Superti-Furga, G., Kirchmair, R., & Valent, P. (2017). Nilotinib-induced vasculopathy: identification of vascular endothelial cells as a primary target site. Leukemia, 31(11), 2388–2397. https://doi.org/10.1038/leu.2017.245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kantarjian, H. M., Cortes, J. E., Kim, D. W., Khoury, H. J., Brümmendorf, T. H., Porkka, K., Martinelli, G., Durrant, S., Leip, E., Kelly, V., Turnbull, K., Besson, N., & Gambacorti-Passerini, C. (2014). Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood, 123(9), 1309–1318. https://doi.org/10.1182/blood-2013-07-513937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hasinoff, B. B., & Patel, D. (2020). Mechanisms of the cardiac myocyte-damaging effects of dasatinib. Cardiovascular Toxicology, 20(4), 380–389. https://doi.org/10.1007/s12012-020-09565-7

    Article  CAS  PubMed  Google Scholar 

  81. Lekes, D., Szadvari, I., Krizanova, O., Lopusna, K., Rezuchova, I., Novakova, M., Novakova, Z., Parak, T., & Babula, P. (2016). Nilotinib induces ER stress and cell death in H9c2 cells. Physiological Research, 65(Suppl 4), 505–514. https://doi.org/10.33549/physiolres.933504

    Article  Google Scholar 

  82. Chan, O., Talati, C., Isenalumhe, L., Shams, S., Nodzon, L., Fradley, M., Sweet, K., & Pinilla-Ibarz, J. (2020). Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia. Blood Advances, 4(3), 530–538. https://doi.org/10.1182/bloodadvances.2019000268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Talbert, D. R., Doherty, K. R., Trusk, P. B., Moran, D. M., Shell, S. A., & Bacus, S. (2015). A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicological Sciences: An Official Journal of the Society of Toxicology, 143(1), 147–155. https://doi.org/10.1093/toxsci/kfu215

    Article  CAS  PubMed  Google Scholar 

  84. Paech, F., Mingard, C., Grünig, D., Abegg, V. F., Bouitbir, J., & Krähenbühl, S. (2018). Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib, regorafenib and sorafenib in human hepatic HepG2 cells. Toxicology, 395, 34–44. https://doi.org/10.1016/j.tox.2018.01.005

    Article  CAS  PubMed  Google Scholar 

  85. Hughes, T. P., Mauro, M. J., Cortes, J. E., Minami, H., Rea, D., DeAngelo, D. J., Breccia, M., Goh, Y.-T., Talpaz, M., Hochhaus, A., le Coutre, P., Ottmann, O., Heinrich, M. C., Steegmann, J. L., Deininger, M. W. N., Janssen, J. J. W. M., Mahon, F.-X., Minami, Y., Yeung, D., … Kim, D.-W. (2019). Asciminib in chronic myeloid Leukemia after ABL kinase inhibitor failure. The New England Journal of Medicine, 381(24), 2315–2326. https://doi.org/10.1056/NEJMoa1902328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Rainbolt, T. K., Saunders, J. M., & Wiseman, R. L. (2014). Stress-responsive regulation of mitochondria through the ER unfolded protein response. Trends in endocrinology and metabolism: TEM, 25(10), 528–537. https://doi.org/10.1016/j.tem.2014.06.007

    Article  CAS  PubMed  Google Scholar 

  87. Gao, P., Yang, W., & Sun, L. (2020). Mitochondria-associated endoplasmic reticulum membranes (MAMs) and their prospective roles in kidney disease. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2020/3120539

    Article  PubMed  PubMed Central  Google Scholar 

  88. Malhotra, J. D., & Kaufman, R. J. (2011). ER stress and its functional link to mitochondria: role in cell survival and death. Cold Spring Harbor Perspectives in Biology, 3(9), a004424. https://doi.org/10.1101/cshperspect.a004424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. The Journal of Physiology, 552(Pt 2), 335–344. https://doi.org/10.1113/jphysiol.2003.049478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Rocca, C., De Francesco, E. M., Pasqua, T., Granieri, M. C., De Bartolo, A., Gallo Cantafio, M. E., Muoio, M. G., Gentile, M., Neri, A., Angelone, T., Viglietto, G., & Amodio, N. (2022). Mitochondrial determinants of anti-cancer drug-induced cardiotoxicity. Biomedicines. https://doi.org/10.3390/biomedicines10030520

    Article  PubMed  PubMed Central  Google Scholar 

  91. Liu, Z. W., Zhu, H. T., Chen, K. L., Dong, X., Wei, J., Qiu, C., & Xue, J. H. (2013). Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy. Cardiovascular Diabetology, 12, 158. https://doi.org/10.1186/1475-2840-12-158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ito, Y., Pandey, P., Mishra, N., Kumar, S., Narula, N., Kharbanda, S., Saxena, S., & Kufe, D. (2001). Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis. Molecular and Cellular Biology, 21(18), 6233–6242. https://doi.org/10.1128/mcb.21.18.6233-6242.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Pattacini, L., Mancini, M., Mazzacurati, L., Brusa, G., Benvenuti, M., Martinelli, G., Baccarani, M., & Santucci, M. A. (2004). Endoplasmic reticulum stress initiates apoptotic death induced by STI571 inhibition of p210 bcr-abl tyrosine kinase. Leukemia Research, 28(2), 191–202. https://doi.org/10.1016/s0145-2126(03)00218-2

    Article  CAS  PubMed  Google Scholar 

  94. Zhang, K., & Kaufman, R. J. (2004). Signaling the unfolded protein response from the endoplasmic reticulum. The Journal of Biological Chemistry, 279(25), 25935–25938. https://doi.org/10.1074/jbc.R400008200

    Article  CAS  PubMed  Google Scholar 

  95. Lozhkin, A., Vendrov, A. E., Ramos-Mondragón, R., Canugovi, C., Stevenson, M. D., Herron, T. J., Hummel, S. L., Figueroa, C. A., Bowles, D. E., Isom, L. L., Runge, M. S., & Madamanchi, N. R. (2022). Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics. Redox Biology, 57, 102474. https://doi.org/10.1016/j.redox.2022.102474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Dröse, S., & Brandt, U. (2012). Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Advances in Experimental Medicine and Biology. https://doi.org/10.1007/978-1-4614-3573-0_6

    Article  PubMed  Google Scholar 

  97. Liu, P., Xiang, J. Z., Zhao, L., Yang, L., Hu, B. R., & Fu, Q. (2008). Effect of beta2-adrenergic agonist clenbuterol on ischemia/reperfusion injury in isolated rat hearts and cardiomyocyte apoptosis induced by hydrogen peroxide. Acta Pharmacologica Sinica, 29(6), 661–669. https://doi.org/10.1111/j.1745-7254.2008.00794.x

    Article  CAS  PubMed  Google Scholar 

  98. Steinhorn, B., Sorrentino, A., Badole, S., Bogdanova, Y., Belousov, V., & Michel, T. (2018). Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nature Communications, 9(1), 4044. https://doi.org/10.1038/s41467-018-06533-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Weatherald, J., Bondeelle, L., Chaumais, M. C., Guignabert, C., Savale, L., Jaïs, X., Sitbon, O., Rousselot, P., Humbert, M., Bergeron, A., & Montani, D. (2020). Pulmonary complications of Bcr-Abl tyrosine kinase inhibitors. The European Respiratory Journal. https://doi.org/10.1183/13993003.00279-2020

    Article  PubMed  Google Scholar 

  100. Damiano, S., Montagnaro, S., Puzio, M. V., Severino, L., Pagnini, U., Barbarino, M., Cesari, D., Giordano, A., Florio, S., & Ciarcia, R. (2018). Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells. Journal of Cellular Biochemistry, 119(6), 4845–4854. https://doi.org/10.1002/jcb.26686

    Article  CAS  PubMed  Google Scholar 

  101. Green, D. E., & Tzagoloff, A. (1966). The mitochondrial electron transfer chain. Archives of Biochemistry and Biophysics, 116(1), 293–304. https://doi.org/10.1016/0003-9861(66)90036-1

    Article  CAS  PubMed  Google Scholar 

  102. Chen, Q., Vazquez, E. J., Moghaddas, S., Hoppel, C. L., & Lesnefsky, E. J. (2003). Production of reactive oxygen species by mitochondria: Central role of complex III. The Journal of Biological Chemistry, 278(38), 36027–36031. https://doi.org/10.1074/jbc.M304854200

    Article  CAS  PubMed  Google Scholar 

  103. Morciano, G., Naumova, N., Koprowski, P., Valente, S., Sardão, V. A., Potes, Y., Rimessi, A., Wieckowski, M. R., & Oliveira, P. J. (2021). The mitochondrial permeability transition pore: An evolving concept critical for cell life and death. Biological Reviews of the Cambridge Philosophical Society, 96(6), 2489–2521. https://doi.org/10.1111/brv.12764

    Article  CAS  PubMed  Google Scholar 

  104. Kwong, J. Q., & Molkentin, J. D. (2015). Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metabolism, 21(2), 206–214. https://doi.org/10.1016/j.cmet.2014.12.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91(4), 479–489. https://doi.org/10.1016/s0092-8674(00)80434-1

    Article  CAS  PubMed  Google Scholar 

  106. Yang, Q., Zhang, C., Wei, H., Meng, Z., Li, G., Xu, Y., & Chen, Y. (2017). Caspase-independent pathway is related to nilotinib cytotoxicity in cultured cardiomyocytes. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 42(6), 2182–2193. https://doi.org/10.1159/000479993

    Article  CAS  PubMed  Google Scholar 

  107. Davis, R. J. (2000). Signal transduction by the JNK group of MAP kinases. Cell, 103(2), 239–252. https://doi.org/10.1016/s0092-8674(00)00116-1

    Article  CAS  PubMed  Google Scholar 

  108. Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H. P., & Ron, D. (2000). Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science (New York, N.Y.), 287(5453), 664–666. https://doi.org/10.1126/science.287.5453.664

    Article  CAS  PubMed  Google Scholar 

  109. Chambers, J. W., & LoGrasso, P. V. (2011). Mitochondrial c-Jun N-terminal kinase (JNK) signaling initiates physiological changes resulting in amplification of reactive oxygen species generation. The Journal of Biological Chemistry, 286(18), 16052–16062. https://doi.org/10.1074/jbc.M111.223602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yang, Q., Wen, L., Meng, Z., & Chen, Y. (2018). Blockage of endoplasmic reticulum stress attenuates nilotinib-induced cardiotoxicity by inhibition of the Akt-GSK3β-Nox4 signaling. European Journal of Pharmacology, 822, 85–94. https://doi.org/10.1016/j.ejphar.2018.01.011

    Article  CAS  PubMed  Google Scholar 

  111. Chambers, T. P., Santiesteban, L., Gomez, D., & Chambers, J. W. (2017). Sab mediates mitochondrial dysfunction involved in imatinib mesylate-induced cardiotoxicity. Toxicology, 382, 24–35. https://doi.org/10.1016/j.tox.2017.03.006

    Article  CAS  PubMed  Google Scholar 

  112. Chaar, M., Kamta, J., & Ait-Oudhia, S. (2018). Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities. OncoTargets and Therapy, 11, 6227–6237. https://doi.org/10.2147/ott.S170138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Freebern, W. J., Fang, H. S., Slade, M. D., Wells, S., Canale, J., Megill, J., Grubor, B., Shi, H., Fletcher, A., Lombardo, L., Levesque, P., Lee, F. Y., & Sasseville, V. G. (2007). In vitro cardiotoxicity potential comparative assessments of chronic myelogenous leukemia tyrosine kinase inhibitor therapies: Dasatinib imatinib and nilotinib. Blood, 110(11), 4582. https://doi.org/10.1182/blood.V110.11.4582.4582

    Article  Google Scholar 

  114. Wolf, A., Couttet, P., Dong, M., Grenet, O., Heron, M., Junker, U., Laengle, U., Ledieu, D., Marrer, E., Nussher, A., Persohn, E., Pognan, F., Rivière, G. J., Roth, D. R., Trendelenburg, C., Tsao, J., & Roman, D. (2010). Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies. Leukemia Research, 34(9), 1180–1188. https://doi.org/10.1016/j.leukres.2010.01.004

    Article  CAS  PubMed  Google Scholar 

  115. Hasinoff, B. B., Patel, D., & Wu, X. (2017). The myocyte-damaging effects of the BCR-ABL1-targeted tyrosine kinase inhibitors increase with potency and decrease with specificity. Cardiovascular Toxicology, 17(3), 297–306. https://doi.org/10.1007/s12012-016-9386-7

    Article  CAS  PubMed  Google Scholar 

  116. Kobayashi, S., Lackey, T., Huang, Y., Bisping, E., Pu, W. T., Boxer, L. M., & Liang, Q. (2006). Transcription factor gata4 regulates cardiac BCL2 gene expression in vitro and in vivo. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 20(6), 800–802. https://doi.org/10.1096/fj.05-5426fje

    Article  CAS  PubMed  Google Scholar 

  117. Sarszegi, Z., Bognar, E., Gaszner, B., Kónyi, A., Gallyas, F., Jr., Sumegi, B., & Berente, Z. (2012). BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Molecular and Cellular Biochemistry, 365(1–2), 129–137. https://doi.org/10.1007/s11010-012-1252-8

    Article  CAS  PubMed  Google Scholar 

  118. Xu, Z., Jin, Y., Yan, H., Gao, Z., Xu, B., Yang, B., He, Q., Shi, Q., & Luo, P. (2018). High-mobility group box 1 protein-mediated necroptosis contributes to dasatinib-induced cardiotoxicity. Toxicology Letters, 296, 39–47. https://doi.org/10.1016/j.toxlet.2018.08.003

    Article  CAS  PubMed  Google Scholar 

  119. Alsaad, A. M. S. (2018). Dasatinib induces gene expression of CYP1A1, CYP1B1, and cardiac hypertrophy markers (BNP, β-MHC) in rat cardiomyocyte H9c2 cells. Toxicology Mechanisms and Methods, 28(9), 678–684. https://doi.org/10.1080/15376516.2018.1497746

    Article  CAS  PubMed  Google Scholar 

  120. Madonna, R., Pieragostino, D., Cufaro, M. C., Del Boccio, P., Pucci, A., Mattii, L., Doria, V., Cadeddu Dessalvi, C., Zucchi, R., Mercuro, G., & De Caterina, R. (2022). Sex-related differential susceptibility to ponatinib cardiotoxicity and differential modulation of the Notch1 signalling pathway in a murine model. Journal of Cellular and Molecular Medicine, 26(5), 1380–1391. https://doi.org/10.1111/jcmm.17008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Singh, A. P., Glennon, M. S., Umbarkar, P., Gupte, M., Galindo, C. L., Zhang, Q., Force, T., Becker, J. R., & Lal, H. (2019). Ponatinib-induced cardiotoxicity: Delineating the signalling mechanisms and potential rescue strategies. Cardiovascular Research, 115(5), 966–977. https://doi.org/10.1093/cvr/cvz006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Sharma, A., Burridge, P. W., McKeithan, W. L., Serrano, R., Shukla, P., Sayed, N., Churko, J. M., Kitani, T., Wu, H. D., Holmstrom, A., Matsa, E., Zhang, Y., Kumar, A., Fan, A. C., del Alamo, J. C., Wu, S. M., Moslehi, J. J., Mercola, M., & Wu, J. C. (2017). High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.aaf2584

    Article  PubMed  PubMed Central  Google Scholar 

  123. Latifi, Y., Moccetti, F., Wu, M., Xie, A., Packwood, W., Qi, Y., Ozawa, K., Shentu, W. H., Brown, E., Shirai, T., McCarty, O. J., Ruggeri, Z., Moslehi, J., Chen, J. M., Druker, B. J., Lopez, J. A., & Lindner, J. R. (2019). Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood, 133(14), 1597–1606. https://doi.org/10.1182/blood-2018-10-881557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hadzijusufovic, E., Kirchmair, R., Theurl, M., Gamperl, S., Lener, D., Gutmann, C., Stanzl, U., Kirsch, A., Frank, S., & Valent, P. (2016). Ponatinib exerts multiple effects on vascular endothelial cells: Possible mechanisms and explanations for the adverse vascular events seen in CML patients treated with ponatinib. Blood, 128(22), 1883. https://doi.org/10.1182/blood.V128.22.1883.1883

    Article  Google Scholar 

  125. Durand, M. J., Hader, S. N., Derayunan, A., Zinkevich, N., McIntosh, J. J., & Beyer, A. M. (2020). BCR-ABL tyrosine kinase inhibitors promote pathological changes in dilator phenotype in the human microvasculature. Microcirculation. https://doi.org/10.1111/micc.12625

    Article  PubMed  PubMed Central  Google Scholar 

  126. Zhou, S. B., Wang, J., & Liu, H. (2016). Lead compound optimization strategy(5) – reducing the hERG cardiac toxicity in drug development. Yao xue xue bao = Acta pharmaceutica Sinica, 51(10), 1530–1539.

    PubMed  Google Scholar 

  127. Hasinoff, B. B., & Patel, D. (2010). Mechanisms of myocyte cytotoxicity induced by the multikinase inhibitor sorafenib. Cardiovascular Toxicology, 10(1), 1–8. https://doi.org/10.1007/s12012-009-9056-0

    Article  CAS  PubMed  Google Scholar 

  128. Aghel, N., Delgado, D. H., & Lipton, J. H. (2017). Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: Preventive strategies and cardiovascular surveillance. Vascular Health and Risk Management, 13, 293–303. https://doi.org/10.2147/vhrm.S108874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Özgür Yurttaş, N., & Eşkazan, A. E. (2018). Dasatinib-induced pulmonary arterial hypertension. British Journal of Clinical Pharmacology, 84(5), 835–845. https://doi.org/10.1111/bcp.13508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Oikonomou, E. K., Kokkinidis, D. G., Kampaktsis, P. N., Amir, E. A., Marwick, T. H., Gupta, D., & Thavendiranathan, P. (2019). Assessment of prognostic value of left ventricular global longitudinal strain for early prediction of chemotherapy-induced cardiotoxicity: A systematic review and meta-analysis. JAMA Cardiology, 4(10), 1007–1018. https://doi.org/10.1001/jamacardio.2019.2952

    Article  PubMed  PubMed Central  Google Scholar 

  131. Novo, G., Di Lisi, D., Bronte, E., Macaione, F., Accurso, V., Badalamenti, G., Rinaldi, G., Siragusa, S., Novo, S., & Russo, A. (2020). Cardiovascular toxicity in cancer patients treated with tyrosine kinase inhibitors: A real-world single-center experience. Oncology, 98(7), 445–451. https://doi.org/10.1159/000505486

    Article  CAS  PubMed  Google Scholar 

  132. Thavendiranathan, P., Negishi, T., Somerset, E., Negishi, K., Penicka, M., Lemieux, J., Aakhus, S., Miyazaki, S., Shirazi, M., Galderisi, M., & Marwick, T. H. (2021). Strain-guided management of potentially cardiotoxic cancer therapy. Journal of the American College of Cardiology, 77(4), 392–401. https://doi.org/10.1016/j.jacc.2020.11.020

    Article  CAS  PubMed  Google Scholar 

  133. Breccia, M., Pregno, P., Spallarossa, P., Arboscello, E., Ciceri, F., Giorgi, M., Grossi, A., Mallardo, M., Nodari, S., Ottolini, S., Sala, C., Tortorella, G., Rosti, G., Pane, F., Minotti, G., & Baccarani, M. (2017). Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: An expert opinion. Annals of Hematology, 96(4), 549–558. https://doi.org/10.1007/s00277-016-2820-x

    Article  CAS  PubMed  Google Scholar 

  134. Caocci, G., Mulas, O., Abruzzese, E., Luciano, L., Iurlo, A., Attolico, I., Castagnetti, F., Galimberti, S., Sgherza, N., Bonifacio, M., Annunziata, M., Gozzini, A., Orlandi, E. M., Stagno, F., Binotto, G., Pregno, P., Fozza, C., Trawinska, M. M., De Gregorio, F., … Breccia, M. (2019). Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart. Hematological Oncology, 37(3), 296–302. https://doi.org/10.1002/hon.2606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Caocci, G., Mulas, O., Capodanno, I., Bonifacio, M., Annunziata, M., Galimberti, S., Luciano, L., Tiribelli, M., Martino, B., Castagnetti, F., Binotto, G., Pregno, P., Stagno, F., Abruzzese, E., Bocchia, M., Gozzini, A., Albano, F., Fozza, C., Luzi, D., … La Nasa, G. (2021). Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib. Annals of Hematology, 100(8), 2005–2014. https://doi.org/10.1007/s00277-020-04392-w

    Article  CAS  PubMed  Google Scholar 

  136. Di Lisi, D., Madaudo, C., Alagna, G., Santoro, M., Rossetto, L., Siragusa, S., & Novo, G. (2022). The new HFA/ICOS risk assessment tool to identify patients with chronic myeloid leukaemia at high risk of cardiotoxicity. ESC Heart Failure, 9(3), 1914–1919. https://doi.org/10.1002/ehf2.13897

    Article  PubMed  PubMed Central  Google Scholar 

  137. Fernández, A., Sanguino, A., Peng, Z., Ozturk, E., Chen, J., Crespo, A., Wulf, S., Shavrin, A., Qin, C., Ma, J., Trent, J., Lin, Y., Han, H. D., Mangala, L. S., Bankson, J. A., Gelovani, J., Samarel, A., Bornmann, W., Sood, A. K., & Lopez-Berestein, G. (2007). An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic. The Journal of Clinical Investigation, 117(12), 4044–4054. https://doi.org/10.1172/jci32373

    Article  PubMed  PubMed Central  Google Scholar 

  138. Demetri, G. D. (2007). Structural reengineering of imatinib to decrease cardiac risk in cancer therapy. Journal of Clinical Investigation, 117(12), 3650–3653. https://doi.org/10.1172/jci34252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Hnatiuk, A. P., Bruyneel, A. A. N., Tailor, D., Pandrala, M., Dheeraj, A., Li, W., Serrano, R., Feyen, D. A. M., Vu, M. M., Amatya, P., Gupta, S., Nakauchi, Y., Morgado, I., Wiebking, V., Liao, R., Porteus, M. H., Majeti, R., Malhotra, S. V., & Mercola, M. (2022). Reengineering Ponatinib to Minimize Cardiovascular Toxicity. Cancer Research, 82(15), 2777–2791. https://doi.org/10.1158/0008-5472.CAN-21-3652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Guo, Y., Wang, X., Jia, P., You, Y., Cheng, Y., Deng, H., Luo, S., & Huang, B. (2020). Ketogenic diet aggravates hypertension via NF-κB-mediated endothelial dysfunction in spontaneously hypertensive rats. Life Sci, 258, 118124. https://doi.org/10.1016/j.lfs.2020.118124

    Article  CAS  PubMed  Google Scholar 

  141. Qu, C., Keijer, J., Adjobo-Hermans, M. J. W., van de Wal, M., Schirris, T., van Karnebeek, C., Pan, Y., & Koopman, W. J. H. (2021). The ketogenic diet as a therapeutic intervention strategy in mitochondrial disease. The International Journal of Biochemistry & Cell Biology, 138, 106050. https://doi.org/10.1016/j.biocel.2021.106050

    Article  CAS  Google Scholar 

  142. Balietti, M., Fattoretti, P., Giorgetti, B., Casoli, T., Di Stefano, G., Solazzi, M., Platano, D., Aicardi, G., & Bertoni-Freddari, C. (2009). A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes. Annals of the New York Academy of Sciences, 1171, 377–384. https://doi.org/10.1111/j.1749-6632.2009.04704.x

    Article  CAS  PubMed  Google Scholar 

  143. Yu, Y., Wang, F., Wang, J., Zhang, D., & Zhao, X. (2020). Ketogenic diet attenuates aging-associated myocardial remodeling and dysfunction in mice. Experimental gerontology, 140, 111058. https://doi.org/10.1016/j.exger.2020.111058

    Article  CAS  PubMed  Google Scholar 

  144. Guo, Y., Zhang, C., Shang, F.-F., Luo, M., You, Y., Zhai, Q., Xia, Y., & Suxin, L. (2020). Ketogenic Diet ameliorates cardiac dysfunction via balancing mitochondrial dynamics and Inhibiting apoptosis apoptosis in type 2 diabetic. Aging Dis, 11(2), 229–240. https://doi.org/10.14336/AD.2019.0510

    Article  PubMed  PubMed Central  Google Scholar 

  145. Lopaschuk, G. D., Karwi, Q. G., Ho, K. L., Pherwani, S., & Ketema, E. B. (2020). Ketone metabolism in the failing heart. Biochimica et Biophysica acta Molecular and cell biology of lipids, 1865(12), 158813. https://doi.org/10.1016/j.bbalip.2020.158813

    Article  CAS  PubMed  Google Scholar 

  146. Al-Zaid, N. S., Dashti, H. M., Mathew, T. C., & Juggi, J. S. (2007). Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia. Acta Cardiologica, 62(4), 381–389.

    Article  PubMed  Google Scholar 

  147. Hasan-Olive, M. M., Lauritzen, K. H., Ali, M., Rasmussen, L. J., Storm-Mathisen, J., & Bergersen, L. H. (2019). A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochemical Research, 44(1), 22–37. https://doi.org/10.1007/s11064-018-2588-6

    Article  CAS  PubMed  Google Scholar 

  148. Ji, L., He, Q., Liu, Y., Deng, Y., Xie, M., Luo, K., Cai, X., Zuo, Y., Wu, W., Li, Q., Zhou, R., & Li, T. (2022). Ketone Body -hydroxybutyrate prevents myocardial oxidative stress in septic cardiomyopathy. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2022/2513837

    Article  PubMed  PubMed Central  Google Scholar 

  149. Ascensão, A., Ferreira, R., & Magalhães, J. (2007). Exercise-induced cardioprotection–biochemical, morphological and functional evidence in whole tissue and isolated mitochondria. International Journal of Cardiology, 117(1), 16–30. https://doi.org/10.1016/j.ijcard.2006.04.076

    Article  PubMed  Google Scholar 

  150. Boulghobra, D., Coste, F., Geny, B., & Reboul, C. (2020). Exercise training protects the heart against ischemia-reperfusion injury: A central role for mitochondria? Free Radical Biology & Medicine, 152, 395–410. https://doi.org/10.1016/j.freeradbiomed.2020.04.005

    Article  CAS  Google Scholar 

  151. Boulghobra, D., Dubois, M., Alpha-Bazin, B., Coste, F., Olmos, M., Gayrard, S., Bornard, I., Meyer, G., Gaillard, J. C., Armengaud, J., & Reboul, C. (2021). Increased protein S-nitrosylation in mitochondria: A key mechanism of exercise-induced cardioprotection. Basic research in cardiology, 116(1), 66. https://doi.org/10.1007/s00395-021-00906-3

    Article  CAS  PubMed  Google Scholar 

  152. Lee, Y., Min, K., Talbert, E. E., Kavazis, A. N., Smuder, A. J., Willis, W. T., & Powers, S. K. (2012). Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Medicine and Science in Sports and Exercise, 44(3), 397–405. https://doi.org/10.1249/MSS.0b013e318231c037

    Article  PubMed  Google Scholar 

  153. Kavazis, A. N., McClung, J. M., Hood, D. A., & Powers, S. K. (2008). Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. American Journal of Physiology Heart and Circulatory Physiology, 294(2), 928–935. https://doi.org/10.1152/ajpheart.01231.2007

    Article  CAS  Google Scholar 

  154. Chang, X., Liu, J., Wang, Y., Guan, X., & Liu, R. (2023). Mitochondrial disorder and treatment of ischemic cardiomyopathy: Potential and advantages of Chinese herbal medicine. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 159, 114171. https://doi.org/10.1016/j.biopha.2022.114171

    Article  Google Scholar 

  155. Jiang, L., Yin, X., Chen, Y. H., Chen, Y., Jiang, W., Zheng, H., Huang, F. Q., Liu, B., Zhou, W., Qi, L. W., & Li, J. (2021). Proteomic analysis reveals ginsenoside Rb1 attenuates myocardial ischemia/reperfusion injury through inhibiting ROS production from mitochondrial complex I. Theranostics, 11(4), 1703–1720. https://doi.org/10.7150/thno.43895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dong, G., Chen, T., Ren, X., Zhang, Z., Huang, W., Liu, L., Luo, P., & Zhou, H. (2016). Rg1 prevents myocardial hypoxia/reoxygenation injury by regulating mitochondrial dynamics imbalance via modulation of glutamate dehydrogenase and mitofusin 2. Mitochondrion. https://doi.org/10.1016/j.mito.2015.11.003

    Article  PubMed  Google Scholar 

  157. Quinsay, M. N., Thomas, R. L., Lee, Y., & Gustafsson, A. B. (2010). Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy, 6(7), 855–862. https://doi.org/10.4161/auto.6.7.13005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Liu, C. S., Chang, J. C., Kuo, S. J., Liu, K. H., Lin, T. T., Cheng, W. L., & Chuang, S. F. (2014). Delivering healthy mitochondria for the therapy of mitochondrial diseases and beyond. The International Journal of Biochemistry & Cell Biology, 53, 141–146. https://doi.org/10.1016/j.biocel.2014.05.009

    Article  CAS  Google Scholar 

  159. McCully, J. D., Cowan, D. B., Pacak, C. A., Toumpoulis, I. K., Dayalan, H., & Levitsky, S. (2009). Injection of isolated mitochondria during early reperfusion for cardioprotection. American Journal Of Physiology Heart and Circulatory Physiology, 296(1), H94-h105. https://doi.org/10.1152/ajpheart.00567.2008

    Article  CAS  PubMed  Google Scholar 

  160. Shin, B., Cowan, D. B., Emani, S. M., Del Nido, P. J., & McCully, J. D. (2017). Mitochondrial Transplantation in Myocardial Ischemia and Reperfusion Injury. Advances in Experimental Medicine and Biology. https://doi.org/10.1007/978-3-319-55330-6_31

    Article  PubMed  Google Scholar 

  161. Ross, D. M., & Hughes, T. P. (2020). Treatment-free remission in patients with chronic myeloid leukaemia. Nature reviews Clinical oncology, 17(8), 493–503. https://doi.org/10.1038/s41571-020-0367-1

    Article  PubMed  Google Scholar 

  162. Sato, E., Iriyama, N., Tokuhira, M., Takaku, T., Ishikawa, M., Nakazato, T., Sugimoto, K. J., Fujita, H., Kimura, Y., Fujioka, I., Asou, N., Komatsu, N., Kizaki, M., Hatta, Y., & Kawaguchi, T. (2020). The EUTOS long-term survival score predicts disease-specific mortality and molecular responses among patients with chronic myeloid leukemia in a practice-based cohort. Cancer Medicine, 9(23), 8931–8939. https://doi.org/10.1002/cam4.3516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F., Clark, R. E., Cortes, J. E., Deininger, M. W., Guilhot, F., Hjorth-Hansen, H., Hughes, T. P., Janssen, J., Kantarjian, H. M., Kim, D. W., Larson, R. A., Lipton, J. H., Mahon, F. X., Mayer, J., … Hehlmann, R. (2020). European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia, 34(4), 966–984. https://doi.org/10.1038/s41375-020-0776-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Vaidya, T., Kamta, J., Chaar, M., Ande, A., & Ait-Oudhia, S. (2018). Systems pharmacological analysis of mitochondrial cardiotoxicity induced by selected tyrosine kinase inhibitors. Journal of Pharmacokinetics and Pharmacodynamics, 45(3), 401–418. https://doi.org/10.1007/s10928-018-9578-9

    Article  CAS  PubMed  Google Scholar 

  165. Henkin, R. I. (2019). Clinical and therapeutic implications of cancer stem cells. New England Journal of Medicine, 381(10), 19. https://doi.org/10.1056/NEJMc1908886

    Article  Google Scholar 

  166. Schoepfer, J., Jahnke, W., Berellini, G., Buonamici, S., Cotesta, S., Cowan-Jacob, S. W., Dodd, S., Drueckes, P., Fabbro, D., Gabriel, T., Groell, J.-M., Grotzfeld, R. M., Hassan, A. Q., Henry, C., Iyer, V., Jones, D., Lombardo, F., Loo, A., Manley, P. W., … Furet, P. (2018). Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1. Journal of Medicinal Chemistry, 61(18), 8120–8135. https://doi.org/10.1021/acs.jmedchem.8b01040

    Article  CAS  PubMed  Google Scholar 

  167. Réa, D., Mauro, M. J., Boquimpani, C., Minami, Y., Lomaia, E., Voloshin, S., Turkina, A., Kim, D. W., Apperley, J. F., Abdo, A., Fogliatto, L. M., Kim, D. D. H., le Coutre, P., Saussele, S., Annunziata, M., Hughes, T. P., Chaudhri, N., Sasaki, K., Chee, L., … Hochhaus, A. (2021). A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood, 138(21), 2031–2041. https://doi.org/10.1182/blood.2020009984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Kantarjian, H., Paul, S., Thakkar, J., & Jabbour, E. (2022). The influence of drug prices, new availability of inexpensive generic imatinib, new approvals, and post-marketing research on the treatment of chronic myeloid leukaemia in the USA. The Lancet Haematology, 9(11), 854–861. https://doi.org/10.1016/s2352-3026(22)00246-0

    Article  CAS  Google Scholar 

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  1. Sheng Sun and Jiqiu Qin have contributed equally to this work.

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  1. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Sheng Sun, Jiqiu Qin, Wenhao Liao, Xiang Gao, Zhoubiao Shang, Dehua Luo & Shaoquan Xiong

  2. Department of Medical Oncology, Hospital of Chengdu University of Traditioanal Chinese Medicine, Chengdu, 610075, Sichuan Province, China

    Sheng Sun & Shaoquan Xiong

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Sun, S., Qin, J., Liao, W. et al. Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies. Cardiovasc Toxicol 23, 233–254 (2023). https://doi.org/10.1007/s12012-023-09800-x

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