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

16 Scopus citations


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
Article number108221
JournalCell Reports
Issue number1
StatePublished - Oct 6 2020


  • PARP inhibitor resistance
  • TGFβR signaling
  • bone marrow microenvironment


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