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Article

Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma

  • Authors:
    • Zhuangwei Lv
    • Chen Xu
    • Zhenzhen Wang
    • Zixian Liu
    • Junna Jiao
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
  • Article Number: 113
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    Published online on: April 4, 2025
       https://doi.org/10.3892/etm.2025.12863
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Abstract

Activation‑induced cytidine deaminase (AID) is an enzyme that plays a crucial role in mediating somatic hypermutation and class‑switch recombination (CSR). It has been found to be associated with aberrant immunoglobulin CSR in activated B‑cell‑like diffuse large B‑cell lymphoma (ABC‑DLBCL). In the present study, MG132, a potent proteasome and calpain inhibitor, induced significant cell death in ABC‑DLBCL cells and inhibited the growth of ABC‑DLBCL cell xenograft tumors. The results also showed that MG132 induced AID accumulation by impairing proteasome degradation of AID. Excessive endogenous AID accumulation was observed in both AID‑deficient and C57/BL6 wild‑type mice treated with MG132, and apparent CSR of IgM to IgG1, IgG3 and IgE. Upon stimulation of cytokines such as LPS and/or IL‑4, ABC‑DLBCL cells also showed a noticeable increase in CSR of IgM to IgG1, IgG3 and IgE with decreased AID protein levels. The present study demonstrates that MG132 can induce AID accumulation, which in turn restores dysfunctional CSR in ABC‑DLBCL. Using MG132 as a tool, the present study elucidates the anti‑lymphoma effect of proteasome inhibitors on ABC‑DLBCL by rescuing the abnormal AID‑induced CSR.
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Copy and paste a formatted citation
Spandidos Publications style
Lv Z, Xu C, Wang Z, Liu Z and Jiao J: Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma. Exp Ther Med 29: 113, 2025.
APA
Lv, Z., Xu, C., Wang, Z., Liu, Z., & Jiao, J. (2025). Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma. Experimental and Therapeutic Medicine, 29, 113. https://doi.org/10.3892/etm.2025.12863
MLA
Lv, Z., Xu, C., Wang, Z., Liu, Z., Jiao, J."Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma". Experimental and Therapeutic Medicine 29.6 (2025): 113.
Chicago
Lv, Z., Xu, C., Wang, Z., Liu, Z., Jiao, J."Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma". Experimental and Therapeutic Medicine 29, no. 6 (2025): 113. https://doi.org/10.3892/etm.2025.12863
Copy and paste a formatted citation
x
Spandidos Publications style
Lv Z, Xu C, Wang Z, Liu Z and Jiao J: Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma. Exp Ther Med 29: 113, 2025.
APA
Lv, Z., Xu, C., Wang, Z., Liu, Z., & Jiao, J. (2025). Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma. Experimental and Therapeutic Medicine, 29, 113. https://doi.org/10.3892/etm.2025.12863
MLA
Lv, Z., Xu, C., Wang, Z., Liu, Z., Jiao, J."Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma". Experimental and Therapeutic Medicine 29.6 (2025): 113.
Chicago
Lv, Z., Xu, C., Wang, Z., Liu, Z., Jiao, J."Excessive activation‑induced cytidine deaminase accumulated by proteasome inhibitors rescues abnormal class switch in activated B‑cell‑like diffuse large B‑cell lymphoma". Experimental and Therapeutic Medicine 29, no. 6 (2025): 113. https://doi.org/10.3892/etm.2025.12863
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