Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition
- 1 January 2021
- journal article
- research article
- Published by Future Medicine Ltd in Epigenomics
- Vol. 13 (2), 129-144
- https://doi.org/10.2217/epi-2020-0189
Abstract
Aim: Waldenström macroglobulinemia (WM) is a low-grade B cell lymphoma characterized by overproduction of monoclonal IgM. To date, there are no therapies that provide a cure for WM patients, and therefore, it is important to explore new therapies. Little is known about the efficiency of epigenetic targeting in WM. Materials & methods: WM cells were treated with BET inhibitors (JQ-1 and I-BET-762) and venetoclax, panobinostat or ibrutinib. Results: BET inhibition reduces growth of WM cells, with little effect on survival. This finding was enhanced by combination therapy, with panobinostat (LBH589) showing the highest synergy. Conclusion: Our studies identify BET inhibitors as effective therapy for WM, and these inhibitors can be enhanced in combination with BCL2 or histone deacetylase inhibition.Keywords
Funding Information
- International Waldenstrom Macrglobulinemia Foundation and Leukemia & Lymphoma Society
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