The expression of cell adhesion molecule 1 and its splicing variants in Sézary cells and cell lines from cutaneous T-cell lymphoma

Mari Yamaguchi, Shin Morizane, Toshihisa Hamada, Tomoko Miyake, Makoto Sugaya, Hiroaki Iwata, Kazuyasu Fujii, Rie Haramoto-Shiratsuki, Yuki Nakagawa, Mayumi Miura, Koichi Ohshima, Kazuhiro Morishita, Takahide Takahashi, Masahide Imada, Ken Okada, Jiro Uehara, Junko Sowa-Osako, Keiji Iwatsuki

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Abstract

Cell adhesion molecule 1 (CADM1) is aberrantly expressed by T-cell neoplasms such as adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides (MF). We studied the expression of CADM1 and its splicing variants in Sézary syndrome (SS), MF, other cutaneous T-cell lymphoma (CTCL), and cell lines derived from T- and B-cell lymphomas. Soluble CADM1 was measured in the patients’ sera. CADM1+ cells in the blood and skin lesions were examined by flow cytometry and immunostaining, respectively. Soluble CADM1 was measured by ELISA, and the splicing variants of CADM1 transcripts were determined by reverse transcriptase-polymerase chain reaction, followed by sequencing. As a result, circulating CADM1+ cells were significantly increased in seven out of 10 patients with SS, ranging from 7.9% to 74.5% of the CD3+CD4+ fractions (median 33.7%; cut-off value 6.5%). The percentages of CADM1+ cells were usually less than those of circulating Sézary cells. CADM1 was expressed, to various degrees, in six of nine T-cell lines derived from SS, MF, ATLL, and anaplastic large cell lymphoma (ALCL), but negative in B-cell lymphoma-derived cell lines. CADM1+ cells were present in the skin infiltrates of MF, SS, ATLL and ALCL. Serum levels of soluble CADM1 were not significantly elevated in SS/MF. Three major splicing variants of CADM1 expressed by neoplastic T-cells contained different combinations of the exons 7, 8, 9 and 11, including a putative oncogenic variant composed of exons 7-8-9-11. In conclusion, CADM1 is frequently expressed in Sézary cells and cell lines from CTCL.

Original languageEnglish
Pages (from-to)967-977
Number of pages11
JournalJournal of Dermatology
Volume46
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • CADM1
  • Sézary syndrome
  • T-cell lines
  • mycosis fungoides
  • splicing variant

ASJC Scopus subject areas

  • Dermatology

Cite this

Yamaguchi, M., Morizane, S., Hamada, T., Miyake, T., Sugaya, M., Iwata, H., Fujii, K., Haramoto-Shiratsuki, R., Nakagawa, Y., Miura, M., Ohshima, K., Morishita, K., Takahashi, T., Imada, M., Okada, K., Uehara, J., Sowa-Osako, J., & Iwatsuki, K. (2019). The expression of cell adhesion molecule 1 and its splicing variants in Sézary cells and cell lines from cutaneous T-cell lymphoma. Journal of Dermatology, 46(11), 967-977. https://doi.org/10.1111/1346-8138.15078