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引用次数: 0
摘要
基因时代为使用个性化治疗方法提供了机会,这种方法的部分基础是靶向体细胞突变基因。例如,携带高复发性 CREBBP 突变的淋巴瘤显示出对 HDAC3 的依赖性,因此选择性抑制 HDAC3 可以逆转 CREBBP 突变的表观遗传效应,阻止淋巴瘤生长,并诱导 MHC II 类表达,使 T 细胞能够识别并杀死淋巴瘤细胞。然而,CREBBP野生型(WT)细胞对这种方法的敏感性较低。在本期《白血病》杂志上,He等人进行了一项全基因组CRISPR筛选,发现GNAS是一种靶点,可以最大限度地提高HDAC3抑制剂对CREBBP WT淋巴瘤的治疗活性。
Silencing GNAS enhances HDAC3i efficacy in CREBBP wild type B cell lymphoma
The genetic era has opened the opportunity of using personalized therapeutic approaches, in part based on targeting genes with somatic mutations. For example, lymphomas harboring the highly recurrent CREBBP mutation show dependency on HDAC3, thus selective inhibition of HDAC3 reversed the epigenetic effects of CREBBP mutation, halted lymphoma growth, and induced MHC class II expression, enabling the T-cells to recognize and kill lymphoma cells. However, CREBBP wild type (WT) cells are less sensitive to this approach. In this issue of Leukemia, He et al. have executed a genome-wide CRISPR screening that identified GNAS as a target to maximize the therapeutic activity of HDAC3 inhibition in CREBBP WT lymphoma.
期刊介绍:
Title: Leukemia
Journal Overview:
Publishes high-quality, peer-reviewed research
Covers all aspects of research and treatment of leukemia and allied diseases
Includes studies of normal hemopoiesis due to comparative relevance
Topics of Interest:
Oncogenes
Growth factors
Stem cells
Leukemia genomics
Cell cycle
Signal transduction
Molecular targets for therapy
And more
Content Types:
Original research articles
Reviews
Letters
Correspondence
Comments elaborating on significant advances and covering topical issues