Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition.
Stephan J MatissekWeiguo HanMona KarbalivandMohamed SayedBrendan M ReillyShayna MallatShimaa M GhazalManit MunshiGuang YangSteven P TreonSarah R WalkerSherine F ElsawaPublished in: Epigenomics (2020)
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.
Keyphrases
- histone deacetylase
- induced apoptosis
- low grade
- cell cycle arrest
- combination therapy
- dna methylation
- newly diagnosed
- end stage renal disease
- gene expression
- endoplasmic reticulum stress
- cell death
- ejection fraction
- chronic kidney disease
- oxidative stress
- drug delivery
- prognostic factors
- diffuse large b cell lymphoma
- chronic lymphocytic leukemia
- patient reported outcomes