Hypoxia-initiated Cysteine-rich protein 61 secretion promotes chemoresistance of acute B lymphoblastic leukemia cells.
Am J Cancer Res
; 14(7): 3388-3403, 2024.
Article
in En
| MEDLINE
| ID: mdl-39113880
ABSTRACT
The drug resistance is a major obstacle in acute B-lymphoblastic leukemia (B-ALL) treatment. Our previous study has indicated that increased levels of Cysteine-rich protein 61 (Cyr61) in the bone marrow can mitigate the chemosensitivity of B-ALL cells, though the specific source of Cyr61 in the bone marrow remains unknown. In this study, we aimed to investigate whether hypoxia can induce Cyr61 production in B-ALL cells, delineates the underlying mechanisms, and evaluates the effect of Cyr61 on the chemosensitivity of B-ALL cells under hypoxia conditions. The results indicate that hypoxia promotes Cyr61 production in B-ALL cells by activating the NF-κB pathway. Increased Cyr61 expression appears to reduce the chemosensitivity of B-ALL cell to vincristine (VCR) and daunorubicin (DNR) through autophagy under hypoxia. Notably, inhibition of Cyr61 restores the chemosensitivity of B-ALL cells to both chemotherapeutic agents. This study is the first time to report that hypoxia decreases the chemosensitivity of B-ALL cells by inducing Cyr61 production, suggesting that targeting Cyr61 or its associated pathways could potentially improve the clinical response of B-ALL patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Am J Cancer Res
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States