Open AccessInhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia
Author(s) -
Carrà Giovanna,
Nicoli Paolo,
Lingua Marcello Francesco,
Maffeo Beatrice,
Cartellà Antonio,
Circosta Paola,
Brancaccio Mara,
Parvis Guido,
Gaidano Valentina,
Guerrasio Angelo,
Saglio Giuseppe,
Taulli Riccardo,
Morotti Alessandro
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14857
Subject(s) - venetoclax , bromodomain , chronic lymphocytic leukemia , cd19 , cancer research , medicine , epigenetics , immunology , biology , antibody , gene , leukemia , genetics
The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19 + lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.