| Added by | liaudet-coopman |
|---|---|
| Group name | EquipeELC |
| Item Type | Journal Article |
| Title | BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice |
| Creator | Hamouda et al. |
| Author | Mohamed-Amine Hamouda |
| Author | Arnaud Jacquel |
| Author | Guillaume Robert |
| Author | Alexandre Puissant |
| Author | Valentine Richez |
| Author | Romeo Cassel |
| Author | Nina Fenouille |
| Author | Sandrine Roulland |
| Author | Jerome Gilleron |
| Author | Emmanuel Griessinger |
| Author | Alix Dubois |
| Author | Beatrice Bailly-Maitre |
| Author | Diogo Goncalves |
| Author | Aude Mallavialle |
| Author | Pascal Colosetti |
| Author | Sandrine Marchetti |
| Author | Martine Amiot |
| Author | Patricia Gomez-Bougie |
| Author | Nathalie Rochet |
| Author | Marcel Deckert |
| Author | Herve Avet-Loiseau |
| Author | Paul Hofman |
| Author | Jean-Michel Karsenti |
| Author | Pierre-Yves Jeandel |
| Author | Claudine Blin-Wakkach |
| Author | Bertrand Nadel |
| Author | Thomas Cluzeau |
| Author | Kenneth C. Anderson |
| Author | Jean-Gabriel Fuzibet |
| Author | Patrick Auberger |
| Abstract | 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. |
| Publication | The Journal of Experimental Medicine |
| Volume | 213 |
| Issue | 9 |
| Pages | 1705-1722 |
| Date | 08 22, 2016 |
| Journal Abbr | J. Exp. Med. |
| Language | eng |
| DOI | 10.1084/jem.20150983 |
| ISSN | 1540-9538 |
| Library Catalog | PubMed |
| Extra | PMID: 27455953 PMCID: PMC4995074 |
| Tags | Animals, bcl-X Protein, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Humans, Hypergammaglobulinemia, Mice, Mice, Inbred C57BL, Mice, Transgenic, Multiple Myeloma, original, Proto-Oncogene Proteins c-bcl-2, Syndecan-1 |
| Date Added | 2018/09/26 - 14:32:48 |
| Date Modified | 2019/05/29 - 12:12:08 |
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