BET 抑制剂表观遗传学靶向治疗巨球蛋白血症细胞与 BCL2 或组蛋白去乙酰化酶抑制协同作用。
Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition.
机构信息
Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, 03824, USA.
Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
出版信息
Epigenomics. 2021 Jan;13(2):129-144. doi: 10.2217/epi-2020-0189. Epub 2020 Dec 24.
Abstract
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. WM cells were treated with BET inhibitors (JQ1 and I-BET-762) and venetoclax, panobinostat or ibrutinib. 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. Our studies identify BET inhibitors as effective therapy for WM, and these inhibitors can be enhanced in combination with BCL2 or histone deacetylase inhibition.
摘要
华氏巨球蛋白血症 (WM) 是一种低级别 B 细胞淋巴瘤，其特征是单克隆 IgM 过度产生。迄今为止，尚无治愈 WM 患者的疗法，因此探索新的疗法非常重要。关于表观遗传靶向在 WM 中的效率知之甚少。 WM 细胞用 BET 抑制剂 (JQ1 和 I-BET-762) 和 venetoclax、panobinostat 或 ibrutinib 处理。BET 抑制可减少 WM 细胞的生长，但对存活几乎没有影响。联合治疗增强了这一发现，panobinostat (LBH589) 显示出最高的协同作用。我们的研究将 BET 抑制剂鉴定为 WM 的有效治疗方法，并且这些抑制剂可以与 BCL2 或组蛋白去乙酰化酶抑制联合增强。
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