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 (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.
Keywords:
BET inhibitors; Waldenström macroglobulinemia; epigenetics; panobinostat; venetoclax.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenine / analogs & derivatives
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Adenine / pharmacology
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Antineoplastic Agents / pharmacology*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Cell Line, Tumor
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Epigenesis, Genetic / drug effects*
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Epigenesis, Genetic / genetics
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Histone Deacetylase Inhibitors / pharmacology*
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Histone Deacetylases / genetics
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Humans
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Lymphoma, B-Cell / drug therapy
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Lymphoma, B-Cell / genetics
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Molecular Targeted Therapy / methods
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Nerve Tissue Proteins / genetics*
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Piperidines / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Receptors, Cell Surface / genetics*
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Sulfonamides / pharmacology
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Waldenstrom Macroglobulinemia / drug therapy*
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Waldenstrom Macroglobulinemia / genetics
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Waldenstrom Macroglobulinemia / metabolism
Substances
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Antineoplastic Agents
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BCL2 protein, human
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Bridged Bicyclo Compounds, Heterocyclic
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DNER protein, human
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Histone Deacetylase Inhibitors
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Nerve Tissue Proteins
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Piperidines
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Cell Surface
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Sulfonamides
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ibrutinib
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Histone Deacetylases
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Adenine
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venetoclax