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.

基因时代为使用个性化治疗方法提供了机会，部分基于针对具有体细胞突变的基因。例如，具有高度复发性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) 细胞对此方法不太敏感。在本期《白血病》中，He 等人。进行了全基因组 CRISPR 筛选，将GNAS确定为靶点，以最大限度地提高CREBBP WT 淋巴瘤中 HDAC3 抑制的治疗活性。