0013706 2025 RIV NL eng J
Burda, Pavel - Hlaváčková, Alžběta - Polívková, Václava - Čuřík, Nikola - Láznička, Adam - Křížková, Jitka - Suttnar, Jiří - Klener, P. - Machová Poláková, Kateřina^G
Imatinib therapy of chronic myeloid leukemia significantly reduces carnitine cell intake, resulting in adverse events.
Molecular metabolism. Vol. 88, no. October (2024), art. no. 102016. ISSN 2212-8778
Institucionální podpora: RVO:00023736
Klíčová slova: CML * OCTN2 * imatinib
Cite Score: 14.700, rok: 2024; SJR: 3.235, rok: 2024; IF: 6.6, rok: 2024
DOI: 10.1016/j.molmet.2024.10201

Anotace: A prominent, safe and efficient therapy for patients with chronic myeloid leukemia (CML) is inhibiting oncogenic protein BCR::ABL1 in a targeted manner with imatinib, a tyrosine kinase inhibitor. A substantial part of patients treated with imatinib report skeletomuscular adverse events affecting their quality of life. OCTN2 membrane transporter is involved in imatinib transportation into the cells. At the same time, the crucial physiological role of OCTN2 is cellular uptake of carnitine which is an essential co-factor for the mitochondrial β-oxidation pathway. This work investigates the impact of imatinib treatment on carnitine intake and energy metabolism of muscle cells. This preclinical experimental study revealed detrimental effect of imatinib on carnitine-mediated energy metabolism of muscle cells providing a possible molecular background of the frequently occurred side effects during imatinib therapy such as fatigue, muscle pain and cramps.