Imatinib mesylate reduces c-MYC expression in double-hit lymphoma cells by suppressing inducible cytidine deaminase.
Imatinib Mesylate
/ pharmacology
Animals
Humans
Cytidine Deaminase
/ genetics
Mice
Proto-Oncogene Proteins c-myc
/ metabolism
Xenograft Model Antitumor Assays
Cell Line, Tumor
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Female
Antineoplastic Agents
/ pharmacology
Translocation, Genetic
Male
Cell Proliferation
/ drug effects
Lymphoma
/ drug therapy
Gene Expression Regulation, Neoplastic
/ drug effects
Activation-induced cytidine deaminase
C-Myc
Diffuse large B-cell lymphoma
Double-hit lymphoma
Imatinib mesylate
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
20 Sep 2024
20 Sep 2024
Historique:
received:
13
08
2024
accepted:
03
09
2024
medline:
20
9
2024
pubmed:
20
9
2024
entrez:
19
9
2024
Statut:
epublish
Résumé
Double-hit lymphoma (DHL) with c-MYC gene translocation is highly aggressive and has a poor prognosis. In DHL cells, activation-induced cytidine deaminase (AID) promotes antibody class switch recombination (CSR), ultimately leading to c-MYC gene translocation caused by Myc/IgH DNA double-strand breaks. However, currently there is still no method to suppress the expression of AID. In this study, we compared the clinical significance of AID expression in DHL, Additionally, two human double-hit lymphoma cell lines were used to analyze the effect of imatinib mesylate on c-MYC in vitro, and the therapeutic effect was also evaluated in xenograft mouse models. Imatinib mesylate downregulated the AID and c-MYC proteins in patients with chronic myelogenous leukemia associated with DHL. In addition, imatinib mesylate reduced AID and c-MYC expression in SU-DHL-4 and OCI-Ly18 DHL cells. Imatinib mesylate exerted significant inhibitory effects on the proliferation and metastasis of SU-DHL-4 and OCI-Ly18 cells. Finally, imatinib mesylate reduced not only tumor burden in DHL mouse models, but also AID and c-MYC expression in vivo. These findings reveal that imatinib mesylate effectively reduces the carcinogenic function of c-MYC in DHL, providing novel strategies for developing therapies targeting c-MYC-driven DHL.
Sections du résumé
BACKGROUND
BACKGROUND
Double-hit lymphoma (DHL) with c-MYC gene translocation is highly aggressive and has a poor prognosis. In DHL cells, activation-induced cytidine deaminase (AID) promotes antibody class switch recombination (CSR), ultimately leading to c-MYC gene translocation caused by Myc/IgH DNA double-strand breaks. However, currently there is still no method to suppress the expression of AID.
METHODS
METHODS
In this study, we compared the clinical significance of AID expression in DHL, Additionally, two human double-hit lymphoma cell lines were used to analyze the effect of imatinib mesylate on c-MYC in vitro, and the therapeutic effect was also evaluated in xenograft mouse models.
RESULTS
RESULTS
Imatinib mesylate downregulated the AID and c-MYC proteins in patients with chronic myelogenous leukemia associated with DHL. In addition, imatinib mesylate reduced AID and c-MYC expression in SU-DHL-4 and OCI-Ly18 DHL cells. Imatinib mesylate exerted significant inhibitory effects on the proliferation and metastasis of SU-DHL-4 and OCI-Ly18 cells. Finally, imatinib mesylate reduced not only tumor burden in DHL mouse models, but also AID and c-MYC expression in vivo.
CONCLUSION
CONCLUSIONS
These findings reveal that imatinib mesylate effectively reduces the carcinogenic function of c-MYC in DHL, providing novel strategies for developing therapies targeting c-MYC-driven DHL.
Identifiants
pubmed: 39299959
doi: 10.1007/s00432-024-05939-4
pii: 10.1007/s00432-024-05939-4
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Cytidine Deaminase
EC 3.5.4.5
Proto-Oncogene Proteins c-myc
0
MYC protein, human
0
AICDA (activation-induced cytidine deaminase)
EC 3.5.4.-
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
426Informations de copyright
© 2024. The Author(s).
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