Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition.

Academic Article

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.
  • Authors

  • Matissek, Stephan J
  • Han, Weiguo
  • Karbalivand, Mona
  • Sayed, Mohamed
  • Reilly, Brendan M
  • Mallat, Shayna
  • Ghazal, Shimaa M
  • Munshi, Manit
  • Yang, Guang
  • Treon, Steven P
  • Walker, Sarah
  • Elsawa, Sherine
  • Status

    Publication Date

  • January 2021
  • Published In

  • Epigenomics  Journal
  • Keywords

  • Adenine
  • Antineoplastic Agents
  • BET inhibitors
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Humans
  • Lymphoma, B-Cell
  • Molecular Targeted Therapy
  • Nerve Tissue Proteins
  • Piperidines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cell Surface
  • Sulfonamides
  • Waldenstrom Macroglobulinemia
  • Waldenström macroglobulinemia
  • epigenetics
  • panobinostat
  • venetoclax
  • Digital Object Identifier (doi)

    Start Page

  • 129
  • End Page

  • 144
  • Volume

  • 13
  • Issue

  • 2