LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL

Salma Parvin, Ariel Ramirez-Labrada, Shlomzion Aumann, Xiao Qing Lu, Natalia Weich, Gabriel Santiago, Elena M. Cortizas, Eden Sharabi, Yu Zhang, Isidro Sanchez-Garcia, Andrew J. Gentles, Evan Roberts, Daniel Bilbao-Cortes, Francisco Vega, Jennifer R. Chapman, Ramiro E. Verdun, Izidore S. Lossos

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)237-249.e6
JournalCancer Cell
Issue number3
StatePublished - Sep 16 2019


  • 53BP1
  • BRCA1
  • DNA damage
  • LMO2
  • PARP
  • R-CHOP
  • acute lymphoblastic leukemia
  • diffuse large B cell lymphoma (DLBCL)
  • homologous recombination
  • olaparib
  • synthetic lethality

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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