聚ADP核糖聚合酶
合成致死
癌症研究
同源重组
生物
聚合酶
PARP抑制剂
DNA修复
分子生物学
弥漫性大B细胞淋巴瘤
PARP1
杀伤力
细胞生物学
DNA
遗传学
作者
Salma Parvin,Ariel Ramírez-Labrada,Shlomzion Aumann,Lu Xiao,Natalia Weich,Gabriel E. Santiago,Elena M. Cortizas,Eden Sharabi,Yu Zhang,Isidro Sánchez-Garcı́a,Andrew J. Gentles,Evan R. Roberts,Daniel Bilbao,Francisco Vega,Jennifer R. Chapman,Ramiro E. Verdún,Izidore S. Lossos
出处
期刊:Cancer Cell
[Elsevier]
日期:2019-09-01
卷期号:36 (3): 237-249.e6
被引量:44
标识
DOI:10.1016/j.ccell.2019.07.007
摘要
Deficiency in DNA double-strand break (DSB) repair mechanisms has been widely exploited for the treatment of different malignances, including homologous recombination (HR)-deficient breast and ovarian cancers. Here we demonstrate that diffuse large B cell lymphomas (DLBCLs) expressing LMO2 protein are functionally deficient in HR-mediated DSB repair. Mechanistically, LMO2 inhibits BRCA1 recruitment to DSBs by interacting with 53BP1 during repair. Similar to BRCA1-deficient cells, LMO2-positive DLBCLs and T cell acute lymphoblastic leukemia (T-ALL) cells exhibit a high sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Furthermore, chemotherapy and PARP inhibitors synergize to inhibit the growth of LMO2-positive tumors. Together, our results reveal that LMO2 expression predicts HR deficiency and the potential therapeutic use of PARP inhibitors in DLBCL and T-ALL.
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