ArticleCancer cell2019
LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 92 citations in OpenAlex.
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Authors and funding
17 authors at 5 institutions in 2 countries.
Salma ParvinDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA.
Ariel Ramirez-LabradaDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Shlomzion AumannDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
XiaoQing LuDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Natalia WeichDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Gabriel SantiagoDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA.
Elena M CortizasDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA.
Eden SharabiDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA.
Yu ZhangDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA.
Isidro Sanchez-GarciaExperimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/ Universidad de Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Andrew J GentlesDepartments of Medicine, and Biomedical Data Science, Stanford University, Stanford, CA, USA.
Evan RobertsSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Daniel Bilbao-CortesSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Francisco VegaSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; Department of Pathology and Laboratory Medicine, Division of Hematopathology, University of Miami, Miami, FL, USA.
Jennifer R ChapmanSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; Department of Pathology and Laboratory Medicine, Division of Hematopathology, University of Miami, Miami, FL, USA.
Ramiro E VerdunDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; Geriatric Research, Education, and Clinical Center, Miami VA Healthcare System, Miami, FL, USA. Electronic address: rverdun@med.miami.edu.
Izidore S LossosDepartment of Medicine, Division of Hematology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue/1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, FL, USA. Electronic address: ilossos@med.miami.edu.
University of Miami · USSylvester Comprehensive Cancer Center · USMiami VA Healthcare System · USStanford University · USUniversidad de Salamanca · ES
Funding
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4MStanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0MTumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI George S. Grills · 2019 to 2026
$24.1MIdentify the Mechanisms of LMO2-Mediated Inhibition of Homologous Recombination and Establish PARP-Targeted Synthetic Lethality as a New Therapy for DLBCLR01CA233945 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LOSSOS, IZIDORE S, VERDUN, RAMIRO ERNESTO · 2019 to 2023
$1.8MRole of TRF2 in DNA recombinationR01GM121595 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI VERDUN, RAMIRO ERNESTO · 2017 to 2021
$1.5MNCATS NIH HHS UL1 TR003142NCI NIH HHS P30 CA124435NCI NIH HHS P30 CA240139NCI NIH HHS R01 CA233945NIGMS NIH HHS R01 GM121595
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.
Indexed as
Adaptor Proteins, Signal TransducingAnimalsAntineoplastic Combined Chemotherapy ProtocolsBiopsyBRCA1 ProteinCell Line, TumorDNA Breaks, Double-StrandedDrug SynergismHumansLIM Domain ProteinsLymphoma, Large B-Cell, DiffuseMicePalatine TonsilPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesAdaptor Proteins, Signal TransducingBRCA1 ProteinBRCA1 protein, humanLIM Domain ProteinsLMO2 protein, humanPARP1 protein, humanPARP2 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesProto-Oncogene ProteinsTP53BP1 protein, humanTumor Suppressor p53-Binding Protein 153BP1acute lymphoblastic leukemiaBRCA1diffuse large B cell lymphoma (DLBCL)DNA damagehomologous recombinationLMO2olaparibPARPR-CHOPsynthetic lethality
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