Ubiquitin and SUMO conjugation as biomarkers of acute myeloid leukemias response to chemotherapies.
Adult
Aged
Antibiotics, Antineoplastic
/ therapeutic use
Antimetabolites, Antineoplastic
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ metabolism
Cell Survival
/ drug effects
Cytarabine
/ therapeutic use
Daunorubicin
/ therapeutic use
Drug Resistance, Multiple
/ drug effects
Drug Resistance, Neoplasm
/ drug effects
HL-60 Cells
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Protein Array Analysis
/ methods
SUMO-1 Protein
/ metabolism
Sumoylation
Treatment Outcome
Ubiquitin
/ metabolism
Young Adult
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
11
10
2019
revised:
06
04
2020
accepted:
06
04
2020
entrez:
19
4
2020
pubmed:
19
4
2020
medline:
8
7
2021
Statut:
epublish
Résumé
Ubiquitin and the ubiquitin-like SUMO are covalently conjugated to thousands of proteins to modulate their function and fate. Many of the enzymes involved in their conjugation are dysregulated in cancers and involved in cancer cell response to therapies. We describe here the identification of biomarkers of the activity of these enzymes and their use to predict acute myeloid leukemias (AML) response to standard chemotherapy (daunorubicin-DNR and cytarabine-Ara-C). We compared the ability of extracts from chemosensitive and chemoresistant AML cells to conjugate ubiquitin or SUMO-1 on 9,000 proteins spotted on protein arrays. We identified 122 proteins whose conjugation by these posttranslational modifiers marks AML resistance to DNR and/or Ara-C. Based on this signature, we defined a statistical score predicting AML patient response to standard chemotherapy. We finally developed a miniaturized assay allowing for easy assessment of modification levels of the selected biomarkers and validated it in patient cell extracts. Thus, our work identifies a new type of ubiquitin-based biomarkers that could be used to predict cancer patient response to treatments.
Identifiants
pubmed: 32303586
pii: 3/6/e201900577
doi: 10.26508/lsa.201900577
pmc: PMC7167290
pii:
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Antimetabolites, Antineoplastic
0
Biomarkers, Tumor
0
SUMO-1 Protein
0
Ubiquitin
0
Cytarabine
04079A1RDZ
Daunorubicin
ZS7284E0ZP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Gâtel et al.
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