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BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice.

Authors: Hamouda, Mohamed-Amine  Jacquel, Arnaud  Robert, Guillaume  Puissant, Alexandre  Richez, Valentine  Cassel, Romeo  Fenouille, Nina  Roulland, Sandrine  Gilleron, Jerome  Griessinger, Emmanuel  Dubois, Alix  Bailly-Maitre, Beatrice  Goncalves, Diogo  Mallavialle, Aude  Colosetti, Pascal  Marchetti, Sandrine  Amiot, Martine  Gomez-Bougie, Patricia  Rochet, Nathalie  Deckert, Marcel  Avet-Loiseau, Herve  Hofman, Paul  Karsenti, Jean-Michel  Jeandel, Pierre-Yves  Blin-Wakkach, Claudine  Nadel, Bertrand  Cluzeau, Thomas  Anderson, Kenneth C  Fuzibet, Jean-Gabriel  Auberger, Patrick  Luciano, Frederic 
Citation: Hamouda MA, etal., J Exp Med. 2016 Aug 22;213(9):1705-22. doi: 10.1084/jem.20150983. Epub 2016 Jul 25.
Pubmed: (View Article at PubMed) PMID:27455953
DOI: Full-text: DOI:10.1084/jem.20150983

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.

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CRRD Object Information
CRRD ID: 14392808
Created: 2019-03-04
Species: All species
Last Modified: 2019-03-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.