Open AccessEpigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition
Author(s) -
Stephan J. Matissek,
Weiguo Han,
Mona Karbalivand,
Mohamed Sayed,
Brendan M. Reilly,
Shayna Mallat,
Shimaa M. Ghazal,
Manit Munshi,
Guang Yang,
Steven P. Treon,
Sarah R. Walker,
Sherine F. Elsawa
Publication year - 2021
Publication title -
epigenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.265
H-Index - 60
eISSN - 1750-1911
pISSN - 1750-192X
DOI - 10.2217/epi-2020-0189
Subject(s) - panobinostat , histone deacetylase , cancer research , waldenstrom macroglobulinemia , epigenetics , vorinostat , bet inhibitor , epigenetic therapy , biology , macroglobulinemia , ibrutinib , histone deacetylase inhibitor , epigenome , lymphoma , histone , bromodomain , immunology , multiple myeloma , dna methylation , leukemia , genetics , gene expression , chronic lymphocytic leukemia , gene
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 (JQ1 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.