作者
King Pan Ng, Axel M Hillmer, Charles TH Chuah, Wen Chun Juan, Tun Kiat Ko, Audrey SM Teo, Pramila N Ariyaratne, Naoto Takahashi, Kenichi Sawada, Yao Fei, Sheila Soh, Wah Heng Lee, John WJ Huang, John C Allen Jr, Xing Yi Woo, Niranjan Nagarajan, Vikrant Kumar, Anbupalam Thalamuthu, Wan Ting Poh, Ai Leen Ang, Hae Tha Mya, Gee Fung How, Li Yi Yang, Liang Piu Koh, Balram Chowbay, Chia-Tien Chang, Veera S Nadarajan, Wee Joo Chng, Hein Than, Lay Cheng Lim, Yeow Tee Goh, Shenli Zhang, Dianne Poh, Patrick Tan, Ju-Ee Seet, Mei-Kim Ang, Noan-Minh Chau, Quan-Sing Ng, Daniel SW Tan, Manabu Soda, Kazutoshi Isobe, Markus M Nöthen, Tien Y Wong, Atif Shahab, Xiaoan Ruan, Valère Cacheux-Rataboul, Wing-Kin Sung, Eng Huat Tan, Yasushi Yatabe, Hiroyuki Mano, Ross A Soo, Tan Min Chin, Wan-Teck Lim, Yijun Ruan, S Tiong Ong
发表日期
2012/4
期刊
Nature medicine
卷号
18
期号
4
页码范围
521-528
出版商
Nature Publishing Group US
简介
Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor–mutated non–small-cell lung cancer (EGFR NSCLC). However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. Using paired-end DNA sequencing, we discovered a common intronic deletion polymorphism in the gene encoding BCL2-like 11 (BIM). BIM is a pro-apoptotic member of the B-cell CLL/lymphoma 2 (BCL2) family of proteins, and its upregulation is required for TKIs to induce apoptosis in kinase-driven cancers. The polymorphism switched BIM splicing from exon 4 to exon 3, which resulted in expression of BIM isoforms lacking the pro-apoptotic BCL2-homology domain 3 (BH3). The polymorphism was sufficient to …
学术搜索中的文章
KP Ng, AM Hillmer, CTH Chuah, WC Juan, TK Ko… - Nature medicine, 2012