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Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma
Author(s) -
Höring Elisabeth,
Montraveta Arnau,
Heine Simon,
Kleih Markus,
Schaaf Lea,
Vöhringer Matthias C.,
EsteveArenys Anna,
Roué Gael,
Colomer Dolors,
Campo Elias,
Ott German,
Aulitzky Walter E.,
Kuip Heiko
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14571
Subject(s) - mcl1 , mantle cell lymphoma , apoptosis , cancer research , lymphoma , cell , chemistry , biology , biochemistry , immunology , downregulation and upregulation , gene
Summary 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.