About: Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy
Creator	Bertoli, Sarah Besson, Arnaud Cartel, Maëlle David, Laure Didier, Christine Gotanègre, Mathilde Manenti, Stéphane Mouchel, Pierre-Luc Sarry, Jean-Emmanuel Mansat-De Mas, Véronique
Source	Medline; PMC
abstract	Resistance of acute myeloid leukemia (AML) to therapeutic agents is frequent. Consequently, the mechanisms leading to this resistance must be understood and addressed. In this paper, we demonstrate that inhibition of deubiquitinylase USP7 significantly reduces cell proliferation in vitro and in vivo, blocks DNA replication progression and increases cell death in AML. Transcriptomic dataset analyses reveal that a USP7 gene signature is highly enriched in cells from AML patients at relapse, as well as in residual blasts from patient-derived xenograft (PDX) models treated with clinically relevant doses of cytarabine, which indicates a relationship between USP7 expression and resistance to therapy. Accordingly, single-cell analysis of AML patient samples at relapse versus at diagnosis showed that a gene signature of the pre-existing subpopulation responsible for relapse is enriched in transcriptomes of patients with a high USP7 level. Furthermore, we found that USP7 interacts and modulates CHK1 protein levels and functions in AML. Finally, we demonstrated that USP7 inhibition acts in synergy with cytarabine to kill AML cell lines and primary cells of patients with high USP7 levels. Altogether, these data demonstrate that USP7 is both a marker of resistance to chemotherapy and a potential therapeutic target in overcoming resistance to treatment.
has issue date	2020-05-23(xsd:dateTime)
bibo:doi	10.1038/s41375-020-0878-x
bibo:pmid	32447346
has license	no-cc
sha1sum (hex)	2d0ffc08531f5b24b7b6ec4acd5b88a808efb547
schema:url	https://doi.org/10.1038/s41375-020-0878-x
resource representing a document's title	Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy
has PubMed Central identifier	PMC7245510
has PubMed identifier	32447346
schema:publication	Leukemia
resource representing a document's body	covid:2d0ffc08531f5b24b7b6ec4acd5b88a808efb547#body_text
is schema:about of	named entity 'target' named entity 'therapeutic' named entity 'addressed' named entity 'reduces' named entity 'level' named entity 'cells' named entity 'SUBPOPULATION' named entity 'TREATMENT' named entity 'USP7' named entity 'POTENTIAL' named entity 'THERAPEUTIC AGENTS' named entity 'PATIENT' named entity 'protein' named entity 'analyses' named entity 'dataset' named entity 'relapse' named entity 'vivo' named entity 'USP7' named entity 'modulates' named entity 'PDX' named entity 'inhibition' named entity 'cell lines' named entity 'enriched' named entity 'AML' named entity 'relapse' named entity 'USP7' named entity 'AML' named entity 'CHK1' named entity 'cell lines' named entity 'AML' named entity 'USP7' named entity 'acute myeloid leukemia' named entity 'HL-60' named entity 'murine' named entity 'CHK1' named entity 'pharmacological' named entity 'transcriptome' named entity 'nuclei' named entity 'busulfan' named entity 'Illumina' named entity 'CHK1' named entity 'FOXO4' named entity 'AML' named entity 'USP7' named entity 'FITC' named entity 'CHK1' named entity 'CHK1' named entity 'blast cells' named entity 'Immunoglobulin' named entity 'USP7' named entity 'transcriptomic' named entity 'antibody' named entity 'antibodies' named entity 'bone marrow' named entity 'HL-60' named entity 'statistical analysis' named entity 'USP7' named entity 'USP7' named entity 'pharmacological' named entity 'mice' named entity 'AML' named entity 'cytarabine' named entity 'USP7' named entity 'leukemic cells' named entity 'bone marrow' named entity 'CD33' named entity 'AML' named entity 'AML' named entity 'AML' named entity 'flow cytometry' named entity 'CHK1' named entity 'AML'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software