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International Journal of Hematology

, Volume 80, Issue 3, pp 254–260 | Cite as

Clinical and Oncologic Implications in Epigenetic Down-Regulation of CD26/ Dipeptidyl Peptidase IV in Adult T-Cell Leukemia Cells

  • Tomohiro Tsuji
  • Kazuyuki Sugahara
  • Kazuto Tsuruda
  • Akiko Uemura
  • Hitomi Harasawa
  • Hiroo Hasegawa
  • Yasuaki Yamada
  • Shimeru Kamihira
  • Yukio Hamaguchi
  • Masao Tomonaga
Article

Abstract

CD26/dipeptidyl peptidase IV (DPPIV), a T-cell-activation antigen, is a 110-kD type II surface glycoprotein expressed on various types of normal cells. CD26/DPPIV is considered a multifunction housekeeping protein. Malignant cells often show altered CD26/DPPIV expression or no CD26/DPPIV expression, thus suggesting a useful marker for assessing some T-cell malignancies. In this study, cell surface protein and messenger RNA expression profiles for CD26/DPPIV were examined in 49 patients with adult T-cell leukemia (ATL), 10 carriers of human T-lymphotropic virus I (HTLV-I), and 4 HTLV-I-infected cell lines to assess the utility of CD26/DPPIV expression as a useful molecular marker for ATL pathology. In contrast to normal lymphocytes, ATL cells and HTLV-I-infected cell lines apparently down-regulated or completely lost the CD26/DPPIV antigen. Furthermore, the positive rate and antigen density for CD26/DPPIV in ATL cells gradually declined along with the advancement of ATL stage. Analysis of genomic DNA and the CD26/DPPIV transcript showed that CD26- ATL cells possessed faintly detected transcripts of the gene that were aberrantly methylated at the CpG islands within the promoter region in parallel with the advancement of ATL, a finding supported by a rescue experiment for transcript reexpression using 5-azacytidine as demethylation agent. Moreover, there was no relationship between loss of CD26/DPPIV and HTLV-I tax expression. These results indicate that ATL cells down-regulate CD26 antigens by means of epigenetic machinery and that this antigen abnormality is a useful molecular marker for the pathology of ATL.

Key words

CD26/DPPIV Down-regulation Epigenetics Adult T-cell leukemia 

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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Tomohiro Tsuji
    • 1
    • 2
  • Kazuyuki Sugahara
    • 1
  • Kazuto Tsuruda
    • 1
  • Akiko Uemura
    • 1
  • Hitomi Harasawa
    • 1
  • Hiroo Hasegawa
    • 1
  • Yasuaki Yamada
    • 1
  • Shimeru Kamihira
    • 1
  • Yukio Hamaguchi
    • 2
  • Masao Tomonaga
    • 3
  1. 1.Department of Laboratory MedicineNagasaki University Graduate School of Biomedical SciencesSakamoto, Nagasaki CityJapan
  2. 2.Sysmex Corporation, KobeNagasaki University Graduate School of Biomedical SciencesSakamoto, Nagasaki CityJapan
  3. 3.Department of Hematology of the Atomic Disease InstituteNagasaki University School of MedicineNagasakiJapan

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