Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Enhancing cell death in B-cell malignancies through targeted inhibition of Bcl-3

Daams, Renée LU ; Tran, Thi Thu Phuong ; Jemaà, Mohamed LU ; Sime, Wondossen LU ; Mickeviciute, Ruta LU ; Ek, Sara LU ; Rönnstrand, Lars LU orcid ; Kazi, Julhash U LU orcid and Massoumi, Ramin LU (2024) In Cell Death & Disease 15(9).
Abstract

The t(14;19)(q32;q13) is a rare recurring translocation found in B-cell lymphoproliferative malignancies, involving the Bcl-3 gene. This chromosomal translocation is often found in patients under the age of 50 and causes a more progressive disease. The Bcl-3 gene encodes a protein belonging to the IκB family of proteins, which tightly regulates NFκB signaling by acting as an activator or repressor of transcription. Previously, we developed a second-generation Bcl-3 inhibitor that could directly interfere with Bcl-3 signaling pathway, resulting in reduced melanoma cell proliferation, invasion, and migration. The present study aimed to investigate the effect of a Bcl-3 inhibitor on B-cell lymphoma and leukemia cells. It was found that... (More)

The t(14;19)(q32;q13) is a rare recurring translocation found in B-cell lymphoproliferative malignancies, involving the Bcl-3 gene. This chromosomal translocation is often found in patients under the age of 50 and causes a more progressive disease. The Bcl-3 gene encodes a protein belonging to the IκB family of proteins, which tightly regulates NFκB signaling by acting as an activator or repressor of transcription. Previously, we developed a second-generation Bcl-3 inhibitor that could directly interfere with Bcl-3 signaling pathway, resulting in reduced melanoma cell proliferation, invasion, and migration. The present study aimed to investigate the effect of a Bcl-3 inhibitor on B-cell lymphoma and leukemia cells. It was found that treatment of cells with this inhibitor caused a decrease in cell proliferation and cell survival. Furthermore, Bcl-3 inhibition in B-cell malignant cells resulted in the loss of mitochondrial membrane potential and functionality, as well as the increased expression of cleaved caspase 3, indicating that cell death occurs through the intrinsic apoptotic pathway. This observation is further supported by reduced expression of cIAP1 protein 1 (cIAP1) upon treatment of cancer cells. Given the current lack of clinical advancements targeting Bcl-3 in oncology, this opens a novel avenue for the development and investigation of highly specific therapeutic interventions against B-cell malignancies.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, B-Cell Lymphoma 3 Protein/metabolism, Apoptosis/drug effects, Cell Line, Tumor, Cell Proliferation/drug effects, Lymphoma, B-Cell/genetics, Membrane Potential, Mitochondrial/drug effects, Signal Transduction/drug effects, Cell Survival/drug effects, Caspase 3/metabolism
in
Cell Death & Disease
volume
15
issue
9
article number
690
publisher
Nature Publishing Group
external identifiers
  • scopus:85204911845
  • pmid:39327470
ISSN
2041-4889
DOI
10.1038/s41419-024-07067-w
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
18035a5e-9b64-48a6-9f6a-aabdc81d4e8c
date added to LUP
2024-09-30 20:13:28
date last changed
2024-10-02 13:49:40
@article{18035a5e-9b64-48a6-9f6a-aabdc81d4e8c,
  abstract     = {{<p>The t(14;19)(q32;q13) is a rare recurring translocation found in B-cell lymphoproliferative malignancies, involving the Bcl-3 gene. This chromosomal translocation is often found in patients under the age of 50 and causes a more progressive disease. The Bcl-3 gene encodes a protein belonging to the IκB family of proteins, which tightly regulates NFκB signaling by acting as an activator or repressor of transcription. Previously, we developed a second-generation Bcl-3 inhibitor that could directly interfere with Bcl-3 signaling pathway, resulting in reduced melanoma cell proliferation, invasion, and migration. The present study aimed to investigate the effect of a Bcl-3 inhibitor on B-cell lymphoma and leukemia cells. It was found that treatment of cells with this inhibitor caused a decrease in cell proliferation and cell survival. Furthermore, Bcl-3 inhibition in B-cell malignant cells resulted in the loss of mitochondrial membrane potential and functionality, as well as the increased expression of cleaved caspase 3, indicating that cell death occurs through the intrinsic apoptotic pathway. This observation is further supported by reduced expression of cIAP1 protein 1 (cIAP1) upon treatment of cancer cells. Given the current lack of clinical advancements targeting Bcl-3 in oncology, this opens a novel avenue for the development and investigation of highly specific therapeutic interventions against B-cell malignancies.</p>}},
  author       = {{Daams, Renée and Tran, Thi Thu Phuong and Jemaà, Mohamed and Sime, Wondossen and Mickeviciute, Ruta and Ek, Sara and Rönnstrand, Lars and Kazi, Julhash U and Massoumi, Ramin}},
  issn         = {{2041-4889}},
  keywords     = {{Humans; B-Cell Lymphoma 3 Protein/metabolism; Apoptosis/drug effects; Cell Line, Tumor; Cell Proliferation/drug effects; Lymphoma, B-Cell/genetics; Membrane Potential, Mitochondrial/drug effects; Signal Transduction/drug effects; Cell Survival/drug effects; Caspase 3/metabolism}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{9}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Cell Death & Disease}},
  title        = {{Enhancing cell death in B-cell malignancies through targeted inhibition of Bcl-3}},
  url          = {{http://dx.doi.org/10.1038/s41419-024-07067-w}},
  doi          = {{10.1038/s41419-024-07067-w}},
  volume       = {{15}},
  year         = {{2024}},
}