作者
Kit I Tong, Sharon Yoon, Keren Isaev, Mehran Bakhtiari, Tracy Lackraj, Michael Y He, Jesse Joynt, Anjali Silva, Maria C Xu, Gilbert G Privé, Housheng Hansen He, Rodger E Tiedemann, Elizabeth A Chavez, Lauren C Chong, Merrill Boyle, David W Scott, Christian Steidl, Robert Kridel
发表日期
2021/10/1
期刊
Clinical Cancer Research
卷号
27
期号
19
页码范围
5401-5414
出版商
American Association for Cancer Research
简介
Purpose
The efficacy of EZH2 inhibition has been modest in the initial clinical exploration of diffuse large B-cell lymphoma (DLBCL), yet EZH2 inhibitors are well tolerated. Herein, we aimed to uncover genetic and pharmacologic opportunities to enhance the clinical efficacy of EZH2 inhibitors in DLBCL.
Experimental Design
We conducted a genome-wide sensitizing CRISPR/Cas9 screen with tazemetostat, a catalytic inhibitor of EZH2. The sensitizing effect of IKZF1 loss of function was then validated and leveraged for combination treatment with lenalidomide. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing analyses were performed to elucidate transcriptomic and epigenetic changes underlying synergy.
Results
We identified IKZF1 knockout as the top candidate for sensitizing DLBCL cells to tazemetostat. Treating cells with …
学术搜索中的文章
KI Tong, S Yoon, K Isaev, M Bakhtiari, T Lackraj, MY He… - Clinical Cancer Research, 2021