Ponatinib Tyrosine Kinase Inhibitor Induces a Thromboinflammatory Response.

Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models. In this study, we examined ponatinib and determined if a calcium channel blocker could ameliorate the pro-thrombotic and pro-inflammatory phenotypes. In vitro treatment of whole human or murine blood with ponatinib and nilotinib increased platelet activation, adhesion and three-dimensional thrombi over time compared with vehicle control or other TKIs. Treatment of wild-type C57BL/6 mice with ponatinib and nilotinib but not imatinib, dasatinib or vehicle control for 4 hours significantly increased thrombus growth following ex vivo perfusion on collagen and FeCl

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Georg Thieme Verlag KG Stuttgart · New York.

Déclaration de conflit d'intérêts

None declared.