A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1+ CLL cells. Issue 3 (20th May 2021)

• Record Type: Journal Article
• Authors: Ghaderi, Amineh; Okhovat, Mohammad‐Ali; Wikanthi, Layung Sekar Sih; Svensson, Ann; Palma, Marzia; Schultz, Johan; Olin, Thomas; Österborg, Anders; Mellstedt, Håkan; Hojjat‐Farsangi, Mohammad
• Is Part Of: EJHaem. Volume 2:Issue 3(2021)
• Page Start: 498
• Page End: 502
• Publication Date: 2021-05-20
• Subjects: BCL‐2 inhibitor -- CLL -- ibrutinib resistance -- ROR1 inhibitor; Hematology -- Periodicals; 616.15
• DOI: 10.1002/jha2.232
• Languages: English
• ISSNs: 2688-6146

Abstract

Abstract: 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.