Ablation of Wnt signaling in bone marrow stromal cells overcomes microenvironment-mediated drug resistance in acute myeloid leukemia.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 Apr 2024
10 Apr 2024
Historique:
received:
14
12
2023
accepted:
03
04
2024
medline:
11
4
2024
pubmed:
11
4
2024
entrez:
10
4
2024
Statut:
epublish
Résumé
The survival of leukemic cells is significantly influenced by the bone marrow microenvironment, where stromal cells play a crucial role. While there has been substantial progress in understanding the mechanisms and pathways involved in this crosstalk, limited data exist regarding the impact of leukemic cells on bone marrow stromal cells and their potential role in drug resistance. In this study, we identify that leukemic cells prime bone marrow stromal cells towards osteoblast lineage and promote drug resistance. This biased differentiation of stroma is accompanied by dysregulation of the canonical Wnt signaling pathway. Inhibition of Wnt signaling in stroma reversed the drug resistance in leukemic cells, which was further validated in leukemic mice models. This study evaluates the critical role of leukemic cells in establishing a drug-resistant niche by influencing the bone marrow stromal cells. Additionally, it highlights the potential of targeting Wnt signaling in the stroma by repurposing an anthelmintic drug to overcome the microenvironment-mediated drug resistance.
Identifiants
pubmed: 38600158
doi: 10.1038/s41598-024-58860-8
pii: 10.1038/s41598-024-58860-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8404Subventions
Organisme : Department of Science and Technology, Ministry of Science and Technology, India
ID : CRG/2019/001214
Organisme : The Wellcome Trust DBT India Alliance
ID : IA/CPHS/18/1/503930
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : BT/COE/34/SP13432/2015
Informations de copyright
© 2024. The Author(s).
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