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Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells

(2017) ONCOTARGET. 8(32). p.52016-52025
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Abstract
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development. Using the immunocompetent 5T33MM model, we demonstrated a significant reduction in BM-plasmacytosis and M-protein levels in mice infected with T. brucei, resulting in an increased survival of these mice. Blocking IFN. could only partially abrogate these effects, suggesting that other mechanisms are involved in the destruction of malignant plasma cells. We found that T. brucei induces intrinsic apoptosis of 5T33MM cells in vivo, and that this was associated with reduced endogenous unfolded protein response (UPR) activation. Interestingly, pharmacological inhibition of IRE1 alpha and PERK was sufficient to induce apoptosis in these cells. Together, these results demonstrate that trypanosome infections can interfere with MM development by suppressing endogenous UPR activation and promoting intrinsic apoptosis.
Keywords
multiple myeloma, T. brucei, ENDOPLASMIC-RETICULUM STRESS, INHIBITOR, CANCER, RESISTANCE

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Citation

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MLA
De Beule, Nathan, et al. “Experimental African Trypanosome Infection Suppresses the Development of Multiple Myeloma in Mice by Inducing Intrinsic Apoptosis of Malignant Plasma Cells.” ONCOTARGET, vol. 8, no. 32, 2017, pp. 52016–25, doi:10.18632/oncotarget.18152.
APA
De Beule, N., Menu, E., Bertrand, M., Favreau, M., De Bruyne, E., Maes, K., … De Trez, C. (2017). Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells. ONCOTARGET, 8(32), 52016–52025. https://doi.org/10.18632/oncotarget.18152
Chicago author-date
De Beule, Nathan, Eline Menu, Mathieu Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, et al. 2017. “Experimental African Trypanosome Infection Suppresses the Development of Multiple Myeloma in Mice by Inducing Intrinsic Apoptosis of Malignant Plasma Cells.” ONCOTARGET 8 (32): 52016–25. https://doi.org/10.18632/oncotarget.18152.
Chicago author-date (all authors)
De Beule, Nathan, Eline Menu, Mathieu Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken, and Carl De Trez. 2017. “Experimental African Trypanosome Infection Suppresses the Development of Multiple Myeloma in Mice by Inducing Intrinsic Apoptosis of Malignant Plasma Cells.” ONCOTARGET 8 (32): 52016–52025. doi:10.18632/oncotarget.18152.
Vancouver
1.
De Beule N, Menu E, Bertrand M, Favreau M, De Bruyne E, Maes K, et al. Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells. ONCOTARGET. 2017;8(32):52016–25.
IEEE
[1]
N. De Beule et al., “Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells,” ONCOTARGET, vol. 8, no. 32, pp. 52016–52025, 2017.
@article{8528137,
  abstract     = {{Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development. Using the immunocompetent 5T33MM model, we demonstrated a significant reduction in BM-plasmacytosis and M-protein levels in mice infected with T. brucei, resulting in an increased survival of these mice. Blocking IFN. could only partially abrogate these effects, suggesting that other mechanisms are involved in the destruction of malignant plasma cells. We found that T. brucei induces intrinsic apoptosis of 5T33MM cells in vivo, and that this was associated with reduced endogenous unfolded protein response (UPR) activation. Interestingly, pharmacological inhibition of IRE1 alpha and PERK was sufficient to induce apoptosis in these cells. Together, these results demonstrate that trypanosome infections can interfere with MM development by suppressing endogenous UPR activation and promoting intrinsic apoptosis.}},
  author       = {{De Beule, Nathan and Menu, Eline and Bertrand, Mathieu and Favreau, Mérédis and De Bruyne, Elke and Maes, Ken and De Veirman, Kim and Radwanska, Magdalena and Samali, Afshin and Magez, Stefan and Vanderkerken, Karin and De Trez, Carl}},
  issn         = {{1949-2553}},
  journal      = {{ONCOTARGET}},
  keywords     = {{multiple myeloma,T. brucei,ENDOPLASMIC-RETICULUM STRESS,INHIBITOR,CANCER,RESISTANCE}},
  language     = {{eng}},
  number       = {{32}},
  pages        = {{52016--52025}},
  title        = {{Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells}},
  url          = {{http://doi.org/10.18632/oncotarget.18152}},
  volume       = {{8}},
  year         = {{2017}},
}

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