Ponatinib reduces viability, migration, and functionality of human endothelial cells

Ayala Gover-Proaktor, Galit Granot*, Saar Shapira, Oshrat Raz, Oren Pasvolsky, Arnon Nagler, Dorit L. Lev, Aida Inbal, Ido Lubin, Pia Raanani, Avi Leader

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function. Furthermore, in HUVECs transfected with VEGF receptor 2 (VEGFR2), the effect of ponatinib on tube formation and on all parameters representing normal endothelial cell function was less prominent than in control cells. This is the first report regarding the pathogenesis of ponatinib-associated VAEs. The antiangiogenic effect of ponatinib, possibly mediated by VEGFR2 inhibition, as shown in our study, is another piece in the intricate puzzle of TKI-associated VAEs.

Original languageEnglish
Pages (from-to)1455-1467
Number of pages13
JournalLeukemia and Lymphoma
Issue number6
StatePublished - 3 Jun 2017


  • Myeloid leukemias and dysplasias
  • cell lines and animal models
  • myeloproliferative disorders


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