A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells

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 d...

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Autores principales: Ghaderi, Amineh, Okhovat, Mohammad‐Ali, Wikanthi, Layung Sekar Sih, Svensson, Ann, Palma, Marzia, Schultz, Johan, Olin, Thomas, Österborg, Anders, Mellstedt, Håkan, Hojjat‐Farsangi, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Short Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176142/
https://www.ncbi.nlm.nih.gov/pubmed/35844694
http://dx.doi.org/10.1002/jha2.232
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author Ghaderi, Amineh
Okhovat, Mohammad‐Ali
Wikanthi, Layung Sekar Sih
Svensson, Ann
Palma, Marzia
Schultz, Johan
Olin, Thomas
Österborg, Anders
Mellstedt, Håkan
Hojjat‐Farsangi, Mohammad
author_facet Ghaderi, Amineh
Okhovat, Mohammad‐Ali
Wikanthi, Layung Sekar Sih
Svensson, Ann
Palma, Marzia
Schultz, Johan
Olin, Thomas
Österborg, Anders
Mellstedt, Håkan
Hojjat‐Farsangi, Mohammad
author_sort Ghaderi, Amineh
collection PubMed
description 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.
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spelling pubmed-91761422022-07-14 A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells Ghaderi, Amineh Okhovat, Mohammad‐Ali Wikanthi, Layung Sekar Sih Svensson, Ann Palma, Marzia Schultz, Johan Olin, Thomas Österborg, Anders Mellstedt, Håkan Hojjat‐Farsangi, Mohammad EJHaem Short Reports 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. John Wiley and Sons Inc. 2021-05-20 /pmc/articles/PMC9176142/ /pubmed/35844694 http://dx.doi.org/10.1002/jha2.232 Text en © 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Reports
Ghaderi, Amineh
Okhovat, Mohammad‐Ali
Wikanthi, Layung Sekar Sih
Svensson, Ann
Palma, Marzia
Schultz, Johan
Olin, Thomas
Österborg, Anders
Mellstedt, Håkan
Hojjat‐Farsangi, Mohammad
A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title_full A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title_fullStr A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title_full_unstemmed A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title_short A ROR1 small molecule inhibitor (KAN0441571C) induced significant apoptosis of ibrutinib‐resistant ROR1(+) CLL cells
title_sort ror1 small molecule inhibitor (kan0441571c) induced significant apoptosis of ibrutinib‐resistant ror1(+) cll cells
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176142/
https://www.ncbi.nlm.nih.gov/pubmed/35844694
http://dx.doi.org/10.1002/jha2.232
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