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Myeloma

Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour

Leukemia volume 15, pages 1127–1132 (2001)Cite this article

Abstract

Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cμ region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.

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Authors and Affiliations

  1. Department of Haematology and Immunology, VUB, Belgium

    MHC Bakkus, K Asosingh, K Vanderkerken & B Van Camp

  2. Department of Physiology, VUB, Belgium

    K Thielemans

  3. Centrum voor menselijke erfelijkheid, KUL, Leuven, Belgium

    A Hagemeijer

  4. Pathology, UIA, Antwerpen, Belgium

    H De Raeve

Authors
  1. MHC Bakkus
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  2. K Asosingh
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  4. K Thielemans
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  5. A Hagemeijer
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  6. H De Raeve
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  7. B Van Camp
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Bakkus, M., Asosingh, K., Vanderkerken, K. et al. Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour. Leukemia 15, 1127–1132 (2001). https://doi.org/10.1038/sj.leu.2402164

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