Inhibition of Bromodomain and Extra-terminal Proteins Increases Sensitivity to Venetoclax in Chronic Lymphocytic Leukaemia

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2019 Dec 11

PMID 31821686

Citations 14

Authors

Giovanna Carra

Paolo Nicoli

Marcello Francesco Lingua

Beatrice Maffeo

Antonio Cartella

Paola Circosta

Mara Brancaccio

Guido Parvis

Valentina Gaidano

Angelo Guerrasio

Giuseppe Saglio

Riccardo Taulli

Alessandro Morotti

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells.

Zheng J, Huang B, Xiao L, Wu M PeerJ. 2024; 12:e17035.

PMID: 38410799 PMC: 10896078. DOI: 10.7717/peerj.17035.

Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.

Wang Z, Zhang Z, Wu Y, Pi Y, Lou S, Liu T Signal Transduct Target Ther. 2023; 8(1):420.

PMID: 37926722 PMC: 10625992. DOI: 10.1038/s41392-023-01647-6.

The role of CD180 in hematological malignancies and inflammatory disorders.

Edwards K, Lydyard P, Kulikova N, Tsertsvadze T, Volpi E, Chiorazzi N Mol Med. 2023; 29(1):97.

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Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers.

Maher N, Mouhssine S, Matti B, Alwan A, Gaidano G Int J Mol Sci. 2023; 24(12).

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A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia.

Smith A, Eiken A, Skupa S, Moore D, Umeta L, Smith L Int J Mol Sci. 2022; 23(12).

PMID: 35743155 PMC: 9224275. DOI: 10.3390/ijms23126712.

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