BCR-ABL Tyrosine Kinase Inhibitors : Which Mechanism(s) May Explain the Risk of Thrombosis?
Imatinib, the first-in-class BCR-ABL tyrosine kinase inhibitor (TKI), had been a revolution for the treatment of chronic myeloid leukemia (CML) and had greatly enhanced patient survival. Second- (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKIs have been developed to be effective against BCR-ABL mutations making imatinib less effective. However, these treatments have been associated with arterial occlusive events. This review gathers clinical data and experiments about the pathophysiology of these arterial occlusive events with BCR-ABL TKIs. Imatinib is associated with very low rates of thrombosis, suggesting a potentially protecting cardiovascular effect of this treatment in patients with BCR-ABL CML. This protective effect might be mediated by decreased platelet secretion and activation, decreased leukocyte recruitment, and anti-inflammatory or antifibrotic effects. Clinical data have guided mechanistic studies toward alteration of platelet functions and atherosclerosis development, which might be secondary to metabolism impairment. Dasatinib, nilotinib, and ponatinib affect endothelial cells and might induce atherogenesis through increased vascular permeability. Nilotinib also impairs platelet functions and induces hyperglycemia and dyslipidemia that might contribute to atherosclerosis development. Description of the pathophysiology of arterial thrombotic events is necessary to implement risk minimization strategies.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2018 |
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Erschienen: |
2018 |
Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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Enthalten in: |
TH open : companion journal to thrombosis and haemostasis - 2(2018), 1 vom: 17. Jan., Seite e68-e88 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Haguet, Hélène [VerfasserIn] |
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Links: |
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Themen: |
Arterial thrombotic events |
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Anmerkungen: |
Date Revised 11.10.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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doi: |
10.1055/s-0038-1624566 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM298638576 |
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