TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment

Bac Viet Le, Paulina Podszywalow-Bartnicka, Silvia Maifrede, Katherine Sullivan-Reed, Margaret Nieborowska-Skorska, Konstantin Golovine, Juo Chin Yao, Reza Nejati, Kathy Q. Cai, Lisa Beatrice Caruso, Julian Swatler, Michal Dabrowski, Zhaorui Lian, Peter Valent, Elisabeth M. Paietta, Ross L. Levine, Hugo F. Fernandez, Martin S. Tallman, Mark R. Litzow, Jian HuangGrant A. Challen, Daniel Link, Italo Tempera, Mariusz A. Wasik, Katarzyna Piwocka, Tomasz Skorski

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Le et al. show that the TGF-β1-TGFβR kinase-SMAD3 pathway protects leukemia cells from PARP inhibitor (PARPi)-mediated synthetic lethality in the bone marrow microenvironment. The targeting of the TGF-β1 axis restored the sensitivity of leukemia cells to PARPi and prolonged survival of leukemia-bearing mice.

Original languageEnglish (US)
Article number108221
JournalCell reports
Volume33
Issue number1
DOIs
StatePublished - Oct 6 2020

Keywords

  • PARP inhibitor resistance
  • TGFβR signaling
  • bone marrow microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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