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However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that E\u00b5-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, E\u00b5-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. E\u00b5-bcl-b plasmocytes show increased expression of a panel of genes known to be dysregulated in human MM pathogenesis. Treatment of E\u00b5-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 E\u00b5-bcl-b mice as a pertinent model to validate new therapies in MM.<\/jats:p>","DOI":"10.1084\/jem.20150983","type":"journal-article","created":{"date-parts":[[2016,7,25]],"date-time":"2016-07-25T10:12:22Z","timestamp":1469441542000},"page":"1705-1722","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice"],"prefix":"10.1084","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-3397","authenticated-orcid":false,"given":"Mohamed-Amine","family":"Hamouda","sequence":"first","affiliation":[{"name":"Team 2, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1065, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire (C3M), 06204 Nice, France 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