Mechanisms, Clinical Phenotype and Potential Risk Prediction for Cardiovascular Toxicity Induced by Tyrosine Kinase Inhibitors In Chronic Myeloid Leukemia

Tyrosine kinase inhibitors (TKIs) form the cornerstone of targeted therapy for chronic myeloid leukemia (CML), significantly improving patient prognosis. However, long-term use of TKIs, particularly second-generation (e.g., nilotinib) and third-generation (e.g., ponatinib) drugs, has led to adverse cardiovascular events (CV-AEs). CV-AEs pose a critical challenge to patients' long-term quality of life and treatment adherence. This narrative review systematically elucidates the complex mechanisms underlying TKI-induced cardiovascular toxicity and proposes the "Metabolism-Endothelium-Thrombosis Axis" as a unifying conceptual framework, integrating endothelial dysfunction, metabolic impairment, oxidative stress, inflammatory responses, and abnormal platelet activation into a coherent pathophysiological cascade. These mechanisms collectively contribute to a spectrum of clinical phenotypes. At the clinical management level, identifying individuals at high risk is crucial. Multiple risk prediction models demonstrate predictive value for CV-AEs, particularly arterial occlusive events (AOEs). Future research should focus on elucidating TKI-specific toxicity pathways, validating and optimizing risk prediction models, and exploring effective cardioprotective strategies. Ultimately, this work will maximize cardiovascular risk reduction while preserving antileukemic efficacy.