Nilotinib-induced alterations in endothelial cell function recapitulate clinical vascular phenotypes independent of ABL1.

ABSTRACT: Nilotinib is a highly effective treatment for chronic myeloid leukemia but has been consistently associated with the development of nilotinib-induced arterial disease (NAD) in a subset of patients. To date, which cell types mediate this effect and whether NAD results from on-target mechanisms is unknown. We utilized human induced pluripotent stem cells (hiPSCs) to generate endothelial cells and vascular smooth muscle cells for in vitro study of NAD. We found that nilotinib adversely affects endothelial proliferation and migration, in addition to increasing intracellular nitric oxide. Nilotinib did not alter endothelial barrier function or lipid uptake. No effect of nilotinib was observed in vascular smooth muscle cells, suggesting that NAD is primarily mediated through endothelial cells. T

SUBMITTER: Pinheiro EA 

PROVIDER: S-EPMC10966048 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature