RUNX1/ETO regulates reactive oxygen species (ROS) levels in t(8,21) acute myeloid leukaemia via FLT3 and RAC1.
FLT3
RAC1
RUNX1/ETO
Reactive oxygen species
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
21 Jun 2023
21 Jun 2023
Historique:
received:
10
03
2023
accepted:
08
06
2023
medline:
23
6
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
epublish
Résumé
Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
Identifiants
pubmed: 37341821
doi: 10.1007/s12032-023-02075-w
pii: 10.1007/s12032-023-02075-w
doi:
Substances chimiques
Core Binding Factor Alpha 2 Subunit
0
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Oncogene Proteins, Fusion
0
rac1 GTP-Binding Protein
EC 3.6.5.2
RAC1 protein, human
0
Reactive Oxygen Species
0
RUNX1 protein, human
0
RUNX1T1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
208Subventions
Organisme : Universiti Sains Malaysia
ID : 1001/CIPPT/813064
Organisme : Universiti Sains Malaysia
ID : 1001/CIPPT/8012265
Organisme : Ministry of Higher Education, Malaysia
ID : FRGS/1/2018/SKK08/USM/02/8
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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