KEY TAKEAWAYS
- The study aimed to investigate the impact of Cyr61 on chemosensitivity in B-ALL cells and elucidate its regulatory mechanisms.
- The results showed DNR induces Cyr61 production, reducing B-ALL chemosensitivity, suggesting Cyr61 targeting for enhanced treatment efficacy.
Chemoresistance poses a significant hurdle in acute lymphoblastic leukemia (ALL) therapy. Elevated levels of Cyr61 in ALL patients’ bone marrow contribute to drug resistance. However, Cyr61’s impact on B-ALL cell chemosensitivity and its regulatory mechanisms remain unclear.
Pengchong Shi and the team aimed to investigate the impact of Cyr61 on chemosensitivity in B-ALL cells and elucidate its regulatory mechanisms.
This study utilized Nalm-6 and Reh human B-ALL cell lines. Cyr61 levels were measured through quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The impact of Cyr61 on B-ALL cell chemosensitivity to daunorubicin (DNR) was assessed using cell viability and flow cytometry analyses. Regulatory mechanisms governing Cyr61 production in bone marrow were investigated through qRT-PCR and western blot analysis.
The analysis revealed that knockdown and overexpression of Cyr61 respectively enhanced and reduced B-ALL cells’ chemosensitivity to DNR. Cyr61 suppressed drug-induced apoptosis by elevating B cell lymphoma-2. Notably, DNR triggered DNA damage response and boosted Cyr61 secretion via the ATM-dependent NF-κB pathway in B-ALL cells.
The induction of Cyr61 production by DNR in B-ALL cells, along with the resultant decrease in chemosensitivity due to increased Cyr61 levels, suggests that targeting Cyr61 or the associated ATM signaling pathway could be a promising strategy to improve the chemosensitivity of B-ALL patients.
Research was supported by Natural Science Foundation of Fujian Province, Fujian Provincial Health Technology Project, and Fujian province Joint Funds for the innovation of science and Technology.
Source: https://pubmed.ncbi.nlm.nih.gov/38530432/
Shi, P., Lin, Z., Song, Y. et al. “Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity.” J Cancer Res Clin Oncol 150, 159 (2024). https://doi.org/10.1007/s00432-024-05692-8.
