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Myeloma

Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma

Leukemia volume 17, pages 1650–1657 (2003)Cite this article

Abstract

Chromosomal band 1p34–36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sγ3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

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Acknowledgements

We thank Ms C Fukuyama and C Nakagawa for their skillful technical assistance. This work was supported in part by a Grant for S Iida and R Ueda from the Ministry of Education, Science, Sports and Culture, Japan and a Research Grant of the Princess Takamatsu Cancer Research Fund for S Iida.

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Authors and Affiliations

  1. Department of Internal Medicine(II) and Molecular Science, Nagoya City University Graduate School of Medical Science, Nagoya, Japan

    Y Hayami, S Iida, I Hanamura, M Kato, H Komatsu & R Ueda

  2. Aichi Blood Disease Research Foundation, Seto, Japan

    Y Hayami

  3. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    N Nakazawa & M Taniwaki

  4. Third Department of Internal Medicine, Akita University Medical School, Akita, Japan

    I Miura

  5. Department of Pediatrics and Pathology/Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    B J Dave

  6. Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA

    W G Sanger

  7. Harvard Institute of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    B Lim

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Hayami, Y., Iida, S., Nakazawa, N. et al. Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma. Leukemia 17, 1650–1657 (2003). https://doi.org/10.1038/sj.leu.2403026

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