| Autor: |
Hong Zhang, Dale L. Greiner, Leonard D. Shultz, James E. Bradner, Andrew M. Evens, Rachel M. Gerstein, Sally E. Trabucco |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6523178 |
| Popis: |
Purpose: Approximately 50% of patients with diffuse large B-cell lymphoma (DLBCL) enter long-term remission after standard chemotherapy. Patients with DLBCL who do not respond to chemotherapy have few treatment options. There remains a critical need to identify effective and targeted therapeutics for DLBCL.Experimental Design: Recent studies have highlighted the incidence of increased c-MYC protein in DLBCL and the correlation between high levels of c-MYC protein and poor survival prognosis of patients with DLBCL, suggesting that c-MYC is a compelling target for DLBCL therapy. The small molecule JQ1 suppresses c-MYC expression through inhibition of the bromodomain and extra-terminal (BET) family of bromodomain proteins. We investigated whether JQ1 can inhibit proliferation of DLBCL cells in culture and xenograft models in vivo.Results: We show that JQ1 at nanomolar concentrations efficiently inhibited proliferation of human DLBCL cells in a dose-dependent manner regardless of their molecular subtypes, suggesting a broad effect of JQ1 in DLBCL. The initial G1 arrest induced by JQ1 treatment in DLBCL cells was followed by either apoptosis or senescence. The expression of c-MYC was suppressed as a result of JQ1 treatment from the natural, chromosomally translocated, or amplified loci. Furthermore, JQ1 treatment significantly suppressed growth of DLBCL cells engrafted in mice and improved survival of engrafted mice.Conclusion: Our results demonstrate that inhibition of the BET family of bromodomain proteins by JQ1 has potential clinical use in the treatment of DLBCL. Clin Cancer Res; 21(1); 113–22. ©2014 AACR.See related commentary by Mottok and Gascoyne, p. 4 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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