Retinoic acid and proteotoxic stress induce AML cell death overcoming stromal cell protection.
AML
Actin cytoskeleton
Bone marrow stromal cells
ER stress
Oxidative stress
Proteotoxic stress
Tumor microenvironment
YAP
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
31 Aug 2023
31 Aug 2023
Historique:
received:
16
05
2023
accepted:
10
08
2023
medline:
4
9
2023
pubmed:
1
9
2023
entrez:
31
8
2023
Statut:
epublish
Résumé
Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A). We treated FLT3-ITD The combination RBA exerts strong cytotoxic activity on FLT3-ITD Our findings strengthen our previous work indicating induction of proteotoxic stress as a possible strategy in FLT3-ITD
Sections du résumé
BACKGROUND
BACKGROUND
Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A).
METHODS
METHODS
We treated FLT3-ITD
RESULTS
RESULTS
The combination RBA exerts strong cytotoxic activity on FLT3-ITD
CONCLUSIONS
CONCLUSIONS
Our findings strengthen our previous work indicating induction of proteotoxic stress as a possible strategy in FLT3-ITD
Identifiants
pubmed: 37653435
doi: 10.1186/s13046-023-02793-z
pii: 10.1186/s13046-023-02793-z
pmc: PMC10469880
doi:
Substances chimiques
Tretinoin
5688UTC01R
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
223Subventions
Organisme : Fondazione AIRC per la ricerca sul cancro ETS
ID : IG 2018-ID 21406
Informations de copyright
© 2023. Italian National Cancer Institute ‘Regina Elena’.
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