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 Huang; Grant A. Challen; Daniel Link; Italo Tempera; Mariusz A. Wasik; Katarzyna Piwocka; Tomasz Skorski

doi:10.1016/j.celrep.2020.108221

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

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18 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 language	English
Article number	108221
Journal	Cell Reports
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2020.108221
State	Published - Oct 6 2020

Keywords

PARP inhibitor resistance
TGFβR signaling
bone marrow microenvironment

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10.1016/j.celrep.2020.108221

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Le, B. V., Podszywalow-Bartnicka, P., Maifrede, S., Sullivan-Reed, K., Nieborowska-Skorska, M., Golovine, K., Yao, J. C., Nejati, R., Cai, K. Q., Caruso, L. B., Swatler, J., Dabrowski, M., Lian, Z., Valent, P., Paietta, E. M., Levine, R. L., Fernandez, H. F., Tallman, M. S., Litzow, M. R., ... Skorski, T. (2020). TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment. Cell Reports, 33(1), Article 108221. https://doi.org/10.1016/j.celrep.2020.108221

@article{679c2e9e03104fab816d7638221bc741,

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 = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = oct,

day = "6",

doi = "10.1016/j.celrep.2020.108221",

language = "English",

volume = "33",

journal = "Cell Reports",

issn = "2211-1247",

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Le, BV, Podszywalow-Bartnicka, P, Maifrede, S, Sullivan-Reed, K, Nieborowska-Skorska, M, Golovine, K, Yao, JC, Nejati, R, Cai, KQ, Caruso, LB, Swatler, J, Dabrowski, M, Lian, Z, Valent, P, Paietta, EM, Levine, RL, Fernandez, HF, Tallman, MS, Litzow, MR, Huang, J, Challen, GA , Link, D, Tempera, I, Wasik, MA, Piwocka, K & Skorski, T 2020, 'TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment', Cell Reports, vol. 33, no. 1, 108221. https://doi.org/10.1016/j.celrep.2020.108221

TY - JOUR

T1 - TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment

AU - Le, Bac Viet

AU - Podszywalow-Bartnicka, Paulina

AU - Maifrede, Silvia

AU - Sullivan-Reed, Katherine

AU - Nieborowska-Skorska, Margaret

AU - Golovine, Konstantin

AU - Yao, Juo Chin

AU - Nejati, Reza

AU - Cai, Kathy Q.

AU - Caruso, Lisa Beatrice

AU - Swatler, Julian

AU - Dabrowski, Michal

AU - Lian, Zhaorui

AU - Valent, Peter

AU - Paietta, Elisabeth M.

AU - Levine, Ross L.

AU - Fernandez, Hugo F.

AU - Tallman, Martin S.

AU - Litzow, Mark R.

AU - Huang, Jian

AU - Challen, Grant A.

AU - Link, Daniel

AU - Tempera, Italo

AU - Wasik, Mariusz A.

AU - Piwocka, Katarzyna

AU - Skorski, Tomasz

PY - 2020/10/6

Y1 - 2020/10/6

N2 - 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.

AB - 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.

KW - PARP inhibitor resistance

KW - TGFβR signaling

KW - bone marrow microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85092277361&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2020.108221

DO - 10.1016/j.celrep.2020.108221

M3 - Article

C2 - 33027668

AN - SCOPUS:85092277361

SN - 2211-1247

VL - 33

JO - Cell Reports

JF - Cell Reports

IS - 1

M1 - 108221

ER -

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

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