Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 177, Issue 4, Pages 557-561Publisher
WILEY
DOI: 10.1111/bjh.14571
Keywords
mantle cell lymphoma; NOXA; MCL1; Dinaciclib; FASNi
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Funding
- Robert Bosch Foundation
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Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA-dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.
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