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Dasatinib induces endothelial dysfunction leading to impaired recovery from ischaemia.

Ayala Gover-ProaktorDorit Leshem-LevSabina Winograd-KatzShirly PartoucheAladin SamaraSaar ShapiraInbar Nardi-AgmonEmanuel HarariAseel YounisAbderrahman NajjarRan KornowskiBenjamin GeigerPia RaananiAvi LeaderGalit Granot
Published in: British journal of haematology (2024)
Chronic myeloid leukaemia (CML) management is complicated by treatment-emergent vascular adverse events seen with tyrosine kinase inhibitors (TKIs) such as nilotinib, dasatinib and ponatinib. Pleural effusion and pulmonary arterial hypertension (PAH) have been associated with dasatinib treatment. Endothelial dysfunction and impaired angiogenesis are hallmarks of PAH. In this study, we explored, at cellular and whole animal levels, the connection between dasatinib exposure and disruption of endothelial barrier integrity and function, leading to impaired angiogenesis. Understanding the mechanisms whereby dasatinib initiates PAH will provide opportunities for intervention and prevention of such adverse effects, and for future development of safer TKIs, thereby improving CML management.
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