| Literature DB >> 31447348 |
Salma Parvin1, Ariel Ramirez-Labrada2, Shlomzion Aumann2, XiaoQing Lu2, Natalia Weich2, Gabriel Santiago1, Elena M Cortizas1, Eden Sharabi1, Yu Zhang1, Isidro Sanchez-Garcia3, Andrew J Gentles4, Evan Roberts5, Daniel Bilbao-Cortes5, Francisco Vega6, Jennifer R Chapman6, Ramiro E Verdun7, Izidore S Lossos8.
Abstract
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.Entities:
Keywords: 53BP1; BRCA1; DNA damage; LMO2; PARP; R-CHOP; acute lymphoblastic leukemia; diffuse large B cell lymphoma (DLBCL); homologous recombination; olaparib; synthetic lethality
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Year: 2019 PMID： 31447348 PMCID： PMC6752209 DOI： 10.1016/j.ccell.2019.07.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743