Abstract：
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.
摘要：
酪氨酸激酶抑制剂（TKIs）如尼洛替尼出现的治疗引起的血管不良事件使慢性髓性白血病（CML）管理变得复杂。达沙替尼和普纳替尼。胸腔积液和肺动脉高压（PAH）与达沙替尼治疗有关。内皮功能障碍和受损的血管生成是PAH的标志。在这项研究中,我们探索，在细胞和整个动物层面，达沙替尼暴露与内皮屏障完整性和功能破坏之间的联系，导致血管生成受损。了解达沙替尼启动PAH的机制将为干预和预防此类不良反应提供机会。为了未来更安全的TKIs的发展，从而改善CML管理。
