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

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 +10 more·2018·Blood

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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Registry

Crossref · 10.1182/blood-2018-05-850339

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30 of 30 references verified0 citation errors · 0 not checkable

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  • Ppm1d loss confers an advantage only in the context of the selective environment of cytotoxic chemotherapy or radiation, but not in steady-state post-transplant conditions.

    “Ppm1d loss confers an advantage only in the context of the selective environment of cytotoxic chemotherapy or radiation, but not in steady-state post-transplant conditions [53,54].”
  • HSCs from mice with mutations in both Tp53 and Ppm1d are able to enter cell cycle despite the presence of DNA damage, leading to a stem cell advantage in the setting of cytotoxic drugs.

    “HSCs from mice with mutations in both Tp53 42 and Ppm1d, a gene encoding a regulator of p53 and other members of the DNA damage response pathway, 43,44 are able to enter cell cycle despite the presence of DNA damage, leading to a stem cell advantage in the setting of cytotoxic drugs.”

    From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [43]

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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.
Venue
Blood
Published
2018-09-13
Volume
132
Issue
11
Pages
1095-1105
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
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
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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