Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications
- Author(s)
- Gao, MY; Georgiou, A; Lin, VS; Jahja, M; White, CA; Anderson, MA; McCormack, MP; Roberts, AW; Huang, DCS; Thijssen, R;
- Details
- Publication Year 2024-10,Volume 205,Issue #4,Page 1389-1394
- Journal Title
- British Journal of Haematology
- Publication Type
- Research article
- 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.
- Publisher
- Wiley
- Keywords
- *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/metabolism; Humans; *Bridged Bicyclo Compounds, Heterocyclic/pharmacology/therapeutic use; *Receptor, Notch1/metabolism/genetics; *Sulfonamides/pharmacology/therapeutic use; *Drug Resistance, Neoplasm; *Antineoplastic Agents/pharmacology/therapeutic use; Signal Transduction/drug effects; apoptosis; bcl‐2; chronic lymphocytic leukaemia; co‐culture; drug resistance
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1111/bjh.19604
- 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.
Creation Date: 2024-10-23 03:11:49
Last Modified: 2024-10-23 03:12:06