BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice
Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptot...
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/107131 |
| _version_ | 1811086821063393280 |
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| author | Fenouille, Nina |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Fenouille, Nina |
| author_sort | Fenouille, Nina |
| collection | MIT |
| description | Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions. In addition, the tumors are serially transplantable in irradiated wild-type mice, underlying the tumoral origin of the disease. Eµ-bcl-b plasmocytes show increased expression of a panel of genes known to be dysregulated in human MM pathogenesis. Treatment of Eµ-bcl-b mice with drugs currently used to treat patients such as melphalan and VELCADE efficiently kills malignant plasmocytes in vivo. Finally, we find that Bcl-B is overexpressed in plasmocytes from MM patients but neither in MGUS patients nor in healthy individuals, suggesting that Bcl-B may drive MM. These findings suggest that Bcl-B could be an important factor in MM disease and pinpoint Eµ-bcl-b mice as a pertinent model to validate new therapies in MM. |
| first_indexed | 2024-09-23T13:35:12Z |
| format | Article |
| id | mit-1721.1/107131 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:35:12Z |
| publishDate | 2017 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1071312022-09-28T14:51:05Z BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice Fenouille, Nina Koch Institute for Integrative Cancer Research at MIT Fenouille, Nina Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions. In addition, the tumors are serially transplantable in irradiated wild-type mice, underlying the tumoral origin of the disease. Eµ-bcl-b plasmocytes show increased expression of a panel of genes known to be dysregulated in human MM pathogenesis. Treatment of Eµ-bcl-b mice with drugs currently used to treat patients such as melphalan and VELCADE efficiently kills malignant plasmocytes in vivo. Finally, we find that Bcl-B is overexpressed in plasmocytes from MM patients but neither in MGUS patients nor in healthy individuals, suggesting that Bcl-B may drive MM. These findings suggest that Bcl-B could be an important factor in MM disease and pinpoint Eµ-bcl-b mice as a pertinent model to validate new therapies in MM. Ligue nationale contre le cancer (France) (Equipe Labellisée Grant R08001AA) Fondation de France (Grant R08080AA) Fondation ARC pour la Recherche sur le Cancer (Grant PGA120140200777) Fondation ARC pour la Recherche sur le Cancer (Project 2015–2016) French Research National Agency (Grant ANR-11-LABX-0028-01) 2017-02-23T19:26:37Z 2017-02-23T19:26:37Z 2016-07 Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/107131 Hamouda, Mohamed-Amine et al. “BCL-B (BCL2L10) Is Overexpressed in Patients Suffering from Multiple Myeloma (MM) and Drives an MM-like Disease in Transgenic Mice.” The Journal of Experimental Medicine 213.9 (2016): 1705–1722. en_US http://dx.doi.org/10.1084/jem.20150983 The Journal of Experimental Medicine Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | Fenouille, Nina BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title_full | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title_fullStr | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title_full_unstemmed | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title_short | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| title_sort | bcl b bcl2l10 is overexpressed in patients suffering from multiple myeloma mm and drives an mm like disease in transgenic mice |
| url | http://hdl.handle.net/1721.1/107131 |
| work_keys_str_mv | AT fenouillenina bclbbcl2l10isoverexpressedinpatientssufferingfrommultiplemyelomammanddrivesanmmlikediseaseintransgenicmice |