Open AccessA ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1 + CLL cells
Author(s) -
Ghaderi Amineh,
Okhovat MohammadAli,
Wikanthi Layung Sekar Sih,
Svensson Ann,
Palma Marzia,
Schultz Johan,
Olin Thomas,
Österborg Anders,
Mellstedt Håkan,
HojjatFarsangi Mohammad
Publication year - 2021
Publication title -
ejhaem
Language(s) - English
Resource type - Journals
ISSN - 2688-6146
DOI - 10.1002/jha2.232
Subject(s) - ibrutinib , bruton's tyrosine kinase , venetoclax , ror1 , cancer research , tyrosine kinase inhibitor , tyrosine kinase , apoptosis , pharmacology , leukemia , medicine , chemistry , chronic lymphocytic leukemia , receptor , biochemistry , cancer , platelet derived growth factor receptor , growth factor
ROR1 – a receptor tyrosine kinase – is overexpressed in CLL. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is clinically effective in CLL but patients may develop resistance. We evaluated the effect of an ROR1 inhibitor, KAN0441571C, in CLL cells from six patients obtained before and after developing resistance to ibrutinib. The ROR1 inhibitor induced apoptosis in ibrutinib‐resistant CLL cells to the same degree as in ibrutinib‐sensitive cells and dephosphorylated ROR1. This was also noted in one patient who became resistant to both ibrutinib and the Bcl‐2 inhibitor venetoclax. The combination of ROR1 inhibitor and venetoclax had a synergistic apoptotic effect on ibrutinib‐resistant cells.