Format

Send to

Choose Destination
J Exp Med. 2016 Aug 22;213(9):1705-22. doi: 10.1084/jem.20150983. Epub 2016 Jul 25.

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

Author information

1
Team 2, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France Equipe Labellisée par la Ligue Nationale Contre le Cancer, 75013 Paris, France.
2
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
3
Team 2, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Service de Médecine Interne, Centre Hospitalier Universitaire de Nice, 06003 Nice, France.
4
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142.
5
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, INSERM U1104, Centre National de la Recherche Scientifique (CNRS) UMR 7280, 13288 Marseille, France.
6
Team 7, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France.
7
Team 4, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France.
8
Team 8, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France.
9
Team 11, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France.
10
Team 10, INSERM U892, 44007 Nantes, France.
11
Université de Nice Sophia-Antipolis, 06000 Nice, France UMR 7277, 06108 Nice, France.
12
Cancer Research Center of Toulouse, UMR 1037, INSERM-Université Toulouse III Paul Sabatier (UPS)-CNRS, 31037 Toulouse, France.
13
Service d'Anatomopathologie, Centre Hospitalier Universitaire de Nice, 06003 Nice, France.
14
Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nice, 06003 Nice, France.
15
Service de Médecine Interne, Centre Hospitalier Universitaire de Nice, 06003 Nice, France.
16
Université de Nice Sophia-Antipolis, 06000 Nice, France CNRS UMR 7370, 06108 Nice, France.
17
Team 2, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France Equipe Labellisée par la Ligue Nationale Contre le Cancer, 75013 Paris, France Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nice, 06003 Nice, France.
18
Team 2, Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Université de Nice Sophia-Antipolis, 06000 Nice, France Equipe Labellisée par la Ligue Nationale Contre le Cancer, 75013 Paris, France fluciano@unice.fr.

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.

PMID:
27455953
PMCID:
PMC4995074
DOI:
10.1084/jem.20150983
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center