BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice
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Hamouda-BCL-B (BCL2L10) is o.pdf
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2.75 MB
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Author(s)
Fenouille, Nina
Date Issued
July 2016
Journal
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
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.
Version
Final published version
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license
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DOI of Published Version
https://doi.org/10.1084/jem.20150983
