Multiple myeloma biology: lessons from the 5TMM models

Authors

  • Karin Vanderkerken,

    Corresponding author
    1. Vrije Universiteit Brussel (VUB), Department of Hematology and Immunology, Belgium.
      Karin Vanderkerken
      Vrije Universiteit Brussel (VUB)
      Department of Hematology and Immunology
      Laarbeeklaan 103
      B-1090 Brussels
      Belgium
      Tel.: 32 2 477 45 73
      Fax: 32 2 477 45 68
      e-mail: Karin.Vanderkerken@vub.ac.be
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  • Kewal Asosingh,

    1. Vrije Universiteit Brussel (VUB), Department of Hematology and Immunology, Belgium.
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  • Peter Croucher,

    1. Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Oxford, UK.
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  • Ben Van Camp

    1. Vrije Universiteit Brussel (VUB), Department of Hematology and Immunology, Belgium.
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Karin Vanderkerken
Vrije Universiteit Brussel (VUB)
Department of Hematology and Immunology
Laarbeeklaan 103
B-1090 Brussels
Belgium
Tel.: 32 2 477 45 73
Fax: 32 2 477 45 68
e-mail: Karin.Vanderkerken@vub.ac.be

Abstract

Summary:  Multiple myeloma (MM) is a B cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable models to study these interactions. These murine models originate from spontaneously developed myeloma in elderly mice, which are propagated by in vivo transfer of the myeloma cells into young syngeneic mice.

In this review we report on studies performed in the 5TMM models with special emphasis on the homing of the myeloma cells, the characterization of the migrating and proliferating clone and the identification of the isotype switch variants. The bone marrow microenvironment was further targeted with osteoprotegerin (OPG) to block the RANK/RANKL/OPG system and with potent bisphosphonates. Both treatments resulted in a significant protection against myeloma-associated bone disease, and they decreased myeloma disease, as evidenced by a lower tumor load and an increased survival of the mice. These different studies demonstrate the strength of these models, not only in unraveling basic biological processes but also in the testing of potentially new therapeutic targets.

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