Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice
- Author
- Tim Pieters (UGent) , Sara T'Sas (UGent) , Stijn Vanhee (UGent) , André Pedro Pinto De Almeida (UGent) , Yasmine Driege (UGent) , Juliette Roels (UGent) , Wouter Van Loocke (UGent) , Willem Daneels (UGent) , Mathijs Baens, Arnaud Marchand, Maaike Van Trimpont (UGent) , Filip Matthijssens (UGent) , Julie Morscio (UGent) , Kelly Lemeire (UGent) , Béatrice Lintermans (UGent) , Lindy Reunes (UGent) , Patrick Chaltin, Fritz Offner (UGent) , Jo Van Dorpe (UGent) , Tino Hochepied (UGent) , Geert Berx (UGent) , Rudi Beyaert (UGent) , Jens Staal (UGent) , Pieter Van Vlierberghe (UGent) and Steven Goossens (UGent)
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- Project
- Abstract
- Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with poor long-term overall survival. Currently, MCL research and development of potential cures is hampered by the lack of good in vivo models. MCL is characterized by recurrent translocations of CCND1 or CCND2, resulting in overexpression of the cell cycle regulators cyclin D1 or D2, respectively. Here, we show, for the first time, that hematopoiesis-specific activation of cyclin D2 is sufficient to drive murine MCL-like lymphoma development. Furthermore, we demonstrate that cyclin D2 overexpression can synergize with loss of p53 to form aggressive and transplantable MCL-like lymphomas. Strikingly, cyclin D2-driven lymphomas display transcriptional, immunophenotypic, and functional similarities with B1a B cells. These MCL-like lymphomas have B1a-specific B cell receptors (BCRs), show elevated BCR and NF-kappa B pathway activation, and display increased MALT1 protease activity. Finally, we provide preclinical evidence that inhibition of MALT1 protease activity, which is essential for the development of early life-derived B1a cells, can be an effective therapeutic strategy to treat MCL.
- Keywords
- Immunology, Immunology and Allergy, MANTLE CELL LYMPHOMA, SET ENRICHMENT ANALYSIS, T-CELL, MOLECULAR PATHOGENESIS, CLASSICAL NEUROLEPTICS, PROTEOLYTIC ACTIVITY, INDIVIDUAL VARIATION, ANTIPSYCHOTIC-DRUGS, HUMAN EQUIVALENT, TRANSGENIC MICE
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8719268
- MLA
- Pieters, Tim, et al. “Cyclin D2 Overexpression Drives B1a-Derived MCL-like Lymphoma in Mice.” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 218, no. 10, 2021, doi:10.1084/jem.20202280.
- APA
- Pieters, T., T’Sas, S., Vanhee, S., Pedro Pinto De Almeida, A., Driege, Y., Roels, J., … Goossens, S. (2021). Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice. JOURNAL OF EXPERIMENTAL MEDICINE, 218(10). https://doi.org/10.1084/jem.20202280
- Chicago author-date
- Pieters, Tim, Sara T’Sas, Stijn Vanhee, André Pedro Pinto De Almeida, Yasmine Driege, Juliette Roels, Wouter Van Loocke, et al. 2021. “Cyclin D2 Overexpression Drives B1a-Derived MCL-like Lymphoma in Mice.” JOURNAL OF EXPERIMENTAL MEDICINE 218 (10). https://doi.org/10.1084/jem.20202280.
- Chicago author-date (all authors)
- Pieters, Tim, Sara T’Sas, Stijn Vanhee, André Pedro Pinto De Almeida, Yasmine Driege, Juliette Roels, Wouter Van Loocke, Willem Daneels, Mathijs Baens, Arnaud Marchand, Maaike Van Trimpont, Filip Matthijssens, Julie Morscio, Kelly Lemeire, Béatrice Lintermans, Lindy Reunes, Patrick Chaltin, Fritz Offner, Jo Van Dorpe, Tino Hochepied, Geert Berx, Rudi Beyaert, Jens Staal, Pieter Van Vlierberghe, and Steven Goossens. 2021. “Cyclin D2 Overexpression Drives B1a-Derived MCL-like Lymphoma in Mice.” JOURNAL OF EXPERIMENTAL MEDICINE 218 (10). doi:10.1084/jem.20202280.
- Vancouver
- 1.Pieters T, T’Sas S, Vanhee S, Pedro Pinto De Almeida A, Driege Y, Roels J, et al. Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice. JOURNAL OF EXPERIMENTAL MEDICINE. 2021;218(10).
- IEEE
- [1]T. Pieters et al., “Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice,” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 218, no. 10, 2021.
@article{8719268,
abstract = {{Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with poor long-term overall survival. Currently, MCL research and development of potential cures is hampered by the lack of good in vivo models. MCL is characterized by recurrent translocations of CCND1 or CCND2, resulting in overexpression of the cell cycle regulators cyclin D1 or D2, respectively. Here, we show, for the first time, that hematopoiesis-specific activation of cyclin D2 is sufficient to drive murine MCL-like lymphoma development. Furthermore, we demonstrate that cyclin D2 overexpression can synergize with loss of p53 to form aggressive and transplantable MCL-like lymphomas. Strikingly, cyclin D2-driven lymphomas display transcriptional, immunophenotypic, and functional similarities with B1a B cells. These MCL-like lymphomas have B1a-specific B cell receptors (BCRs), show elevated BCR and NF-kappa B pathway activation, and display increased MALT1 protease activity. Finally, we provide preclinical evidence that inhibition of MALT1 protease activity, which is essential for the development of early life-derived B1a cells, can be an effective therapeutic strategy to treat MCL.}},
articleno = {{e20202280}},
author = {{Pieters, Tim and T'Sas, Sara and Vanhee, Stijn and Pedro Pinto De Almeida, André and Driege, Yasmine and Roels, Juliette and Van Loocke, Wouter and Daneels, Willem and Baens, Mathijs and Marchand, Arnaud and Van Trimpont, Maaike and Matthijssens, Filip and Morscio, Julie and Lemeire, Kelly and Lintermans, Béatrice and Reunes, Lindy and Chaltin, Patrick and Offner, Fritz and Van Dorpe, Jo and Hochepied, Tino and Berx, Geert and Beyaert, Rudi and Staal, Jens and Van Vlierberghe, Pieter and Goossens, Steven}},
issn = {{0022-1007}},
journal = {{JOURNAL OF EXPERIMENTAL MEDICINE}},
keywords = {{Immunology,Immunology and Allergy,MANTLE CELL LYMPHOMA,SET ENRICHMENT ANALYSIS,T-CELL,MOLECULAR PATHOGENESIS,CLASSICAL NEUROLEPTICS,PROTEOLYTIC ACTIVITY,INDIVIDUAL VARIATION,ANTIPSYCHOTIC-DRUGS,HUMAN EQUIVALENT,TRANSGENIC MICE}},
language = {{eng}},
number = {{10}},
pages = {{24}},
title = {{Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice}},
url = {{http://doi.org/10.1084/jem.20202280}},
volume = {{218}},
year = {{2021}},
}
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