@article{4327034bd68b49668ee340417464122d,
title = "TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment",
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.",
keywords = "PARP inhibitor resistance, TGFβR signaling, bone marrow microenvironment",
author = "Le, {Bac Viet} and Paulina Podszywalow-Bartnicka and Silvia Maifrede and Katherine Sullivan-Reed and Margaret Nieborowska-Skorska and Konstantin Golovine and Yao, {Juo Chin} and Reza Nejati and Cai, {Kathy Q.} and Caruso, {Lisa Beatrice} and Julian Swatler and Michal Dabrowski and Zhaorui Lian and Peter Valent and Paietta, {Elisabeth M.} and Levine, {Ross L.} and Fernandez, {Hugo F.} and Tallman, {Martin S.} and Litzow, {Mark R.} and Jian Huang and Challen, {Grant A.} and Daniel Link and Italo Tempera and Wasik, {Mariusz A.} and Katarzyna Piwocka and Tomasz Skorski",
note = "Funding Information: This work was funded by NIH R01CA186238 , R01CA244044 , and R01CA247707 ; the Leukemia and Lymphoma Society Translational Research Program award 6565-19 ; and the When Everyone Survives Foundation (to T.S.). B.V.L. has been supported by the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement no. 665735 and by the funding from Polish Ministry of Science and Higher Education funds for the implementation of international projects, 2016–2020 (to K.P.). K.S.-R. was supported by T32CA009009035-43 from NIH . P.P.-B. has been supported by the Hollis Brownstein New Investigator Research Grant from the Leukemia Research Foundation (funding cycle 2018–2019) and research grants from the National Science Centre ( 2014/15/D/NZ3/05187 and 2018/30/M/NZ3/00274 ). P.V. was supported by the Austrian Science Fund (FWF) research grants F4701-B28 and F4704-B28 . We thank the Laboratory of Animal Models, Nencki Institute of Experimental Biology, Warsaw for the generation of lentivirally transferred MV4-11 cells. This work was supported by the ANIMOD project within the Team Tech Core Facility Plus program of the Foundation for Polish Science , co-financed by the European Union under the European Regional Development Fund . Funding Information: This work was funded by NIH R01CA186238, R01CA244044, and R01CA247707; the Leukemia and Lymphoma Society Translational Research Program award 6565-19; and the When Everyone Survives Foundation (to T.S.). B.V.L. has been supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement no. 665735 and by the funding from Polish Ministry of Science and Higher Education funds for the implementation of international projects, 2016?2020 (to K.P.). K.S.-R. was supported by T32CA009009035-43 from NIH. P.P.-B. has been supported by the Hollis Brownstein New Investigator Research Grant from the Leukemia Research Foundation (funding cycle 2018?2019) and research grants from the National Science Centre (2014/15/D/NZ3/05187 and 2018/30/M/NZ3/00274). P.V. was supported by the Austrian Science Fund (FWF) research grants F4701-B28 and F4704-B28. We thank the Laboratory of Animal Models, Nencki Institute of Experimental Biology, Warsaw for the generation of lentivirally transferred MV4-11 cells. This work was supported by the ANIMOD project within the Team Tech Core Facility Plus program of the Foundation for Polish Science, co-financed by the European Union under the European Regional Development Fund. B.V.L. P.P.-B. S.M. K.S.-R. M.N.-S. K.G. J.-C.Y. R.N. K.Q.C. J.S. M.D. and Z.L. performed the experiments. E.M.P. provided the genetically characterized AML samples from E1900, and R.L.L. performed the somatic sequencing studies of the E1900 samples. H.F.F. led trial E1900, M.S.T. was the ECOG-ACRIN Leukemia Committee chair when E1900 was activated, and M.R.L. is the current ECOG-ACRIN Leukemia Committee chair. P.V. provided the genetically characterized AML samples. G.A.C. and D.L. provided the genetically modified mice. J.H. supervised Z.L. M.A.W. supervised R.N. and K.Q.C. and critically reviewed the manuscript. T.S. and K.P. designed the studies, supervised the experiments, and wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = oct,
day = "6",
doi = "10.1016/j.celrep.2020.108221",
language = "English (US)",
volume = "33",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}