Mondello Patrizia
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Leukemia. 2024 Oct;38(10):2087-2089. doi: 10.1038/s41375-024-02355-y. Epub 2024 Jul 19.
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.
基因时代开启了使用个性化治疗方法的机会，部分基于靶向具有体细胞突变的基因。例如，携带高度复发性CREBBP突变的淋巴瘤表现出对HDAC3的依赖性，因此选择性抑制HDAC3可逆转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）细胞对这种方法不太敏感。在本期《白血病》杂志中，何等人进行了全基因组CRISPR筛选，确定GNAS是在CREBBP WT淋巴瘤中最大化HDAC3抑制治疗活性的靶点。
