Cited by 225Protein Tyrosine PhosphatasesAcute Myeloid Leukemia ResearchChronic Myeloid Leukemia Treatments

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PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells

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Kahn, Josephine D., Miller, Peter G., Silver, Alexander J., Sellar, Rob S., Bhatt, Shruti, Gibson, Christopher, McConkey, Marie, Adams, Dylan, Mar, Brenton, Mertins, Philipp, Fereshetian, Shaunt, Krug, Karsten, Zhu, Haoling, Letai, Anthony, Carr, Steven A., Doench, John, Jaiswal, Siddhartha, Ebert, Benjamin L.·2018·Blood

DOI 10.1182/blood-2018-05-850339PMC PMC6137556

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Abstract

Key Points Truncating PPM1D mutations confer chemotherapy resistance, leading to the selective expansion of PPM1D-mutant cells in vitro and in vivo. PPM1D inhibitor treatment reverses the chemotherapy-resistance phenotype and selectively kills PPM1D-mutant cells.

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Authors: Kahn, J. D., Miller, P. G., Silver, A. J., Sellar, R. S., Bhatt, S., Gibson, C., McConkey, M., Adams, D., Mar, B., Mertins, P., Fereshetian, S., Krug, K., Zhu, H., Letai, A., Carr, S. A., Doench, J., Jaiswal, S., & Ebert, B. L.
Affiliations: Broad Institute (US)
Brigham and Women's Hospital (US)
Harvard University (US)
Corresponding author: Jaiswal, Siddhartha
Ebert, Benjamin L.
ORCID: Miller, Peter G.
Silver, Alexander J.
Sellar, Rob S.
Bhatt, Shruti
Gibson, Christopher
McConkey, Marie
Mar, Brenton
Mertins, Philipp
Fereshetian, Shaunt
Krug, Karsten
Zhu, Haoling
Letai, Anthony
Carr, Steven A.
Doench, John
Jaiswal, Siddhartha
Ebert, Benjamin L.
Venue: Blood
Publisher: American Society of Hematology
Published: 2018-09-13
Volume: 132
Issue: 11
Pages: 1095-1105
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2018-05-850339
PMC: PMC6137556
OpenAlex: W2810683705
Cited by: 225
References: 30
Citations by year: 2026: 16 · 2025: 24 · 2024: 26 · 2023: 33 · 2022: 38 · 2021: 27 · 2020: 31 · 2019: 24 · 2018: 5
FWCI: 7.73
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Blood (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Heart, Lung, and Blood Institute (R01HL082945, T32HL116324, T32HL066987)
National Cancer Institute (P01CA108631, P50CA206963, P01CA066996)
National Institute of General Medical Sciences (R01GM038627)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords: PPM1D, truncating mutations, chemoresistance, hematopoietic cells, hematologic malignancies, phosphatase
MeSH terms: Protein Phosphatase 2C, Base Sequence, Enzyme Inhibitors, Hematopoietic Stem Cells, Humans, Myeloproliferative Disorders, Neoplasm Proteins, Neoplastic Stem Cells, Sequence Deletion, Drug Resistance, Neoplasm, Hematologic Neoplasms, Cell Line, Tumor, CRISPR-Cas Systems

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PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells

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