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 Huang

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

Research output: Contribution to journal › Article › peer-review

23 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 - https://www.scopus.com/pages/publications/85092277361

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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Keywords

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