Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity

© 2024. The Author(s)..

PURPOSE: Chemoresistance is a major challenge for acute lymphoblastic leukemia (ALL) treatment. Cysteine-rich protein 61 (Cyr61) plays an important role in drug resistance modulation of tumor cells, and Cyr61 levels are increased in the bone marrow of patients with ALL and contribute to ALL cell survival. However, the effect of Cyr61 on B cell acute lymphoblastic leukemia (B-ALL) cell chemosensitivity and the regulatory mechanisms underlying Cyr61 production in bone marrow remain unknown.

METHODS: Nalm-6 and Reh human B-ALL cell lines were used in this study. Cyr61 levels were assessed using quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The effect of Cyr61 on B-ALL cell chemosensitivity to daunorubicin (DNR) was evaluated using cell viability and flow cytometry analyses. The regulatory mechanisms of Cyr61 production in bone marrow were examined using qRT-PCR and western blot analysis.

RESULTS: Cyr61 knockdown and overexpression increased and decreased the chemosensitivity of B-ALL cells to DNR, respectively. Cyr61 attenuated chemotherapeutic drug-induced apoptosis by upregulating B cell lymphoma-2. Notably, DNR induced DNA damage response and increased Cyr61 secretion in B-ALL cells through the ataxia telangiectasia mutated (ATM)-dependent nuclear factor kappa B pathway.

CONCLUSION: DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:150

Enthalten in:

Journal of cancer research and clinical oncology - 150(2024), 3 vom: 26. März, Seite 159

Sprache:

Englisch

Beteiligte Personen:

Shi, Pengchong [VerfasserIn]
Lin, Zhen [VerfasserIn]
Song, Yanfang [VerfasserIn]
Li, Zhaozhong [VerfasserIn]
Zeng, Menglu [VerfasserIn]
Luo, Li [VerfasserIn]
Cao, Yingping [VerfasserIn]
Zhu, Xianjin [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
Chemosensitivity
Cyr61
Cysteine-Rich Protein 61
DNA damage
Journal Article
NF-kappa B

Anmerkungen:

Date Completed 28.03.2024

Date Revised 15.04.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s00432-024-05692-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370199898