Inhibition of the mutated c-KIT kinase in AML1-ETO–positive leukemia cells restores sensitivity to PARP inhibitor

Margaret Nieborowska-Skorska; Elisabeth M. Paietta; Ross L. Levine; Hugo F. Fernandez; Martin S. Tallman; Mark R. Litzow; Tomasz Skorski

doi:10.1182/bloodadvances.2019000756

Inhibition of the mutated c-KIT kinase in AML1-ETO–positive leukemia cells restores sensitivity to PARP inhibitor

Margaret Nieborowska-Skorska
, Elisabeth M. Paietta
, Ross L. Levine
, Hugo F. Fernandez
, Martin S. Tallman
, Mark R. Litzow
, Tomasz Skorski

Temple University
Thomas Jefferson University
State Med. Ctr. of Indust. Medicine
College of Science and Technology
Yeshiva University
Montefiore Health System
New York Medical College
Albert Einstein College of Medicine
Memorial Sloan-Kettering Cancer Center
Memorial Regional Hospital
Northwestern University
Mayo Clinic

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

17 Scopus citations

Abstract

c-KIT activating mutations cause resistance to PARP inhibitor in AML1-ETO–positive leukemias. c-KIT inhibitor avapritinib downregulates BRCA1/2 and DNA-PK catalytic subunit to restore the sensitivity to PARP inhibitor.

Original language	English
Pages (from-to)	4050-4054
Number of pages	5
Journal	Blood advances
Volume	3
Issue number	23
DOIs	https://doi.org/10.1182/bloodadvances.2019000756
State	Published - 2019

Keywords

Cell Line, Tumor
Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors
Humans
Leukemia/drug therapy
Oncogene Proteins, Fusion/antagonists & inhibitors
Poly(ADP-ribose) Polymerase Inhibitors/pharmacology
RUNX1 Translocation Partner 1 Protein/antagonists & inhibitors

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10.1182/bloodadvances.2019000756

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@article{24569673aeaa43d087d8a4586cce8f44,

title = "Inhibition of the mutated c-KIT kinase in AML1-ETO{\textendash}positive leukemia cells restores sensitivity to PARP inhibitor",

abstract = "c-KIT activating mutations cause resistance to PARP inhibitor in AML1-ETO{\textendash}positive leukemias. c-KIT inhibitor avapritinib downregulates BRCA1/2 and DNA-PK catalytic subunit to restore the sensitivity to PARP inhibitor.",

keywords = "Cell Line, Tumor, Core Binding Factor Alpha 2 Subunit/antagonists \& inhibitors, Humans, Leukemia/drug therapy, Oncogene Proteins, Fusion/antagonists \& inhibitors, Poly(ADP-ribose) Polymerase Inhibitors/pharmacology, RUNX1 Translocation Partner 1 Protein/antagonists \& inhibitors",

author = "Margaret Nieborowska-Skorska and Paietta, \{Elisabeth M.\} and Levine, \{Ross L.\} and Fernandez, \{Hugo F.\} and Tallman, \{Martin S.\} and Litzow, \{Mark R.\} and Tomasz Skorski",

year = "2019",

doi = "10.1182/bloodadvances.2019000756",

language = "English",

volume = "3",

pages = "4050--4054",

journal = "Blood advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "23",

}

TY - JOUR

T1 - Inhibition of the mutated c-KIT kinase in AML1-ETO–positive leukemia cells restores sensitivity to PARP inhibitor

AU - Nieborowska-Skorska, Margaret

AU - Paietta, Elisabeth M.

AU - Levine, Ross L.

AU - Fernandez, Hugo F.

AU - Tallman, Martin S.

AU - Litzow, Mark R.

AU - Skorski, Tomasz

PY - 2019

Y1 - 2019

N2 - c-KIT activating mutations cause resistance to PARP inhibitor in AML1-ETO–positive leukemias. c-KIT inhibitor avapritinib downregulates BRCA1/2 and DNA-PK catalytic subunit to restore the sensitivity to PARP inhibitor.

AB - c-KIT activating mutations cause resistance to PARP inhibitor in AML1-ETO–positive leukemias. c-KIT inhibitor avapritinib downregulates BRCA1/2 and DNA-PK catalytic subunit to restore the sensitivity to PARP inhibitor.

KW - Cell Line, Tumor

KW - Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors

KW - Humans

KW - Leukemia/drug therapy

KW - Oncogene Proteins, Fusion/antagonists & inhibitors

KW - Poly(ADP-ribose) Polymerase Inhibitors/pharmacology

KW - RUNX1 Translocation Partner 1 Protein/antagonists & inhibitors

UR - https://www.scopus.com/pages/publications/85076356933

U2 - 10.1182/bloodadvances.2019000756

DO - 10.1182/bloodadvances.2019000756

M3 - Article

C2 - 31816060

SN - 2473-9529

VL - 3

SP - 4050

EP - 4054

JO - Blood advances

JF - Blood advances

IS - 23

ER -

Inhibition of the mutated c-KIT kinase in AML1-ETO–positive leukemia cells restores sensitivity to PARP inhibitor

Abstract

Keywords

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