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

被引：9
作者：
Matissek, Stephan J. [1 ]
Han, Weiguo [1 ]
Karbalivand, Mona [1 ]
Sayed, Mohamed [1 ]
Reilly, Brendan M. [1 ]
Mallat, Shayna [1 ]
Ghazal, Shimaa M. [1 ]
Munshi, Manit [2 ,3 ]
Yang, Guang [2 ,3 ]
Treon, Steven P. [2 ,3 ]
Walker, Sarah R. [1 ]
Elsawa, Sherine F. [1 ]
机构：
[1] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03824 USA
[2] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02215 USA
[3] Harvard Med Sch, Dept Med, Boston, MA 02115 USA
来源：
EPIGENOMICS | 2021年 / 13卷 / 02期
关键词：
BET inhibitors; epigenetics; panobinostat; venetoclax; Waldenströ m macroglobulinemia; BONE-MARROW MICROENVIRONMENT; C-MYC; BROMODOMAIN PROTEINS; MYD88; L265P; IN-VIVO; IBRUTINIB; EXPRESSION; SURVIVAL; LINE; AMPLIFICATION;
D O I：
10.2217/epi-2020-0189
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Aim: Waldenstrom 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.
引用
收藏
页码：129 / 144
页数：16
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