BCL‐2 and MCL1 co‐inhibition enhances glucocorticoid therapy in preclinical models of infant KMT2A‐rearranged acute lymphoblastic leukaemia
Mawar Karsa, Ayu Karsa, Dayna Spurling, Lin Xiao, Emma Ronca, Angelika Bongers, Weiman Gao, Andrew J Gifford, Ali El‐Ayoubi, Laurence C Cheung, Rishi S Kotecha, Richard B Lock, Charis E Teh, Guillaume Lessene, Murray D Norris, Andrew Wei, Michelle Haber, Michelle J Henderson, Donia M Moujalled, Klaa · 2026
Read BCL‐2 and MCL1 co‐inhibition enhances glucocorticoid therapy in preclinical models of infant KMT2A‐rearranged acute lymphoblastic leukaemia by Mawar Karsa, Ayu Karsa, Dayna Spurling, Lin Xiao, Emma Ronca, Angelika Bongers, Weiman Gao, Andrew J Gifford, Ali El‐Ayoubi, Laurence C Cheung, Rishi S Kotecha, Richard B Lock, Charis E Teh, Guillaume Lessene, Murray D Norris, Andrew Wei, Michelle Haber, Michelle J Henderson, Donia M Moujalled, Klaa (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13461956.txt.
Description
Mawar Karsa and co-authors report that blocking two cell survival proteins at once makes standard steroid therapy far deadlier to infant leukemia cells in laboratory models. The disease, KMT2A rearranged acute lymphoblastic leukemia, strikes babies and resists treatment. It depends on the survival protein MCL1, which the rearranged gene switches on directly and which blunts both steroids and the BCL-2 blocker venetoclax. In their 2026 letter, the team combined an MCL1 inhibitor with venetoclax or the steroid dexamethasone in resistant and responsive cell lines.
The MCL1 blocker S63845 paired with either drug killed more effectively than single agents across the viability assays. Adding BCL-2 blockade deepened the effect further, with combination treatment measurably raising the cell death machinery's activation markers, including cleaved caspases. Since high MCL1 marks steroid resistance in infant samples, co inhibition attacks resistance at its root. The dual blockade is a preclinical rationale for trials.
Catalog record
| CREATOR | Mawar Karsa, Ayu Karsa, Dayna Spurling, Lin Xiao, Emma Ronca, Angelika Bongers, Weiman Gao, Andrew J Gifford, Ali El‐Ayoubi, Laurence C Cheung, Rishi S Kotecha, Richard B Lock, Charis E Teh, Guillaume Lessene, Murray D Norris, Andrew Wei, Michelle Haber, Michelle J Henderson, Donia M Moujalled, Klaa |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 40 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |