Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications
Journal Title
British Journal of Haematology
Publication Type
Online publication before print
Abstract
Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 activation, common in CLL, confers adverse prognosis. This study explores the impact of NOTCH1 signalling on venetoclax sensitivity in vitro. Although NOTCH1 activation minimally impaired the susceptibility of CLL cells to venetoclax, ex vivo cell competition studies reveal that cells with constitutive NOTCH1 activation outgrew their wild-type counterparts in the presence of ongoing venetoclax exposure. Our findings suggest that while NOTCH1 activation is insufficient to confer venetoclax refractoriness, there is enhanced potential for cells with NOTCH1 activation to escape and thus become fully resistant to venetoclax.
Keywords
apoptosis; bcl‐2; chronic lymphocytic leukaemia; co‐culture; drug resistance
Department(s)
Clinical Haematology
Open Access at Publisher's Site
https://doi.org/10.1111/bjh.19604
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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