Clinical and Oncologic Implications in Epigenetic Down-regulation of CD26/dipeptidyl Peptidase IV in Adult T-cell Leukemia Cells

Overview

Journal Int J Hematol

Specialty Hematology

Date 2004 Nov 16

PMID 15540901

Citations 13

Authors

Tomohiro Tsuji

Kazuyuki Sugahara

Kazuto Tsuruda

Akiko Uemura

Hitomi Harasawa

Hiroo Hasegawa

Yukio Hamaguchi

Masao Tomonaga

Yasuaki Yamada

Shimeru Kamihira

Affiliations

Soon will be listed here.

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.

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References

Klobusicka M, Babusikova O . Expression of CD26 and DPP IV in T-acute lymphoblastic leukemia: comparison of immunocytochemistry with enzyme cytochemistry. Neoplasma. 2000; 46(5):299-303. View

Abbott C, Baker E, Sutherland G, McCaughan G . Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene. Immunogenetics. 1994; 40(5):331-8. DOI: 10.1007/BF01246674. View

Lambeir A, Proost P, Durinx C, Bal G, Senten K, Augustyns K . Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J Biol Chem. 2001; 276(32):29839-45. DOI: 10.1074/jbc.M103106200. View

Proost P, Struyf S, Schols D, Durinx C, Wuyts A, Lenaerts J . Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha. FEBS Lett. 1998; 432(1-2):73-6. DOI: 10.1016/s0014-5793(98)00830-8. View

Takatsuki K, Matsuoka M, Yamaguchi K . Adult T-cell leukemia in Japan. J Acquir Immune Defic Syndr Hum Retrovirol. 1996; 13 Suppl 1:S15-9. DOI: 10.1097/00042560-199600001-00004. View

Kamihira S, Dateki N, Sugahara K, Hayashi T, Harasawa H, Minami S . Significance of HTLV-1 proviral load quantification by real-time PCR as a surrogate marker for HTLV-1-infected cell count. Clin Lab Haematol. 2003; 25(2):111-7. DOI: 10.1046/j.1365-2257.2003.00503.x. View

Wesley U, Albino A, Tiwari S, Houghton A . A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med. 1999; 190(3):311-22. PMC: 2195594. DOI: 10.1084/jem.190.3.311. View

Bauvois B, De Meester I, Dumont J, Rouillard D, Zhao H, Bosmans E . Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia. Br J Cancer. 1999; 79(7-8):1042-8. PMC: 2362248. DOI: 10.1038/sj.bjc.6690167. View

Kotani T, Aratake Y, Kondo S, Tamura K, OHTAKI S . Expression of functional Fas antigen on adult T-cell leukemia. Leuk Res. 1994; 18(4):305-10. DOI: 10.1016/0145-2126(94)90034-5. View

10.

Boonacker E, van Noorden C . The multifunctional or moonlighting protein CD26/DPPIV. Eur J Cell Biol. 2003; 82(2):53-73. DOI: 10.1078/0171-9335-00302. View

11.

Yamada Y, Fujita M, Suzuki H, Atogami S, Sohda H, Murata K . Established IL-2-dependent double-negative (CD4- CD8-) TCR alpha beta/CD3+ ATL cells: induction of CD4 expression. Br J Haematol. 1994; 88(2):234-41. DOI: 10.1111/j.1365-2141.1994.tb05012.x. View

12.

Martin M, Huguet J, Centelles J, Franco R . Expression of ecto-adenosine deaminase and CD26 in human T cells triggered by the TCR-CD3 complex. Possible role of adenosine deaminase as costimulatory molecule. J Immunol. 1995; 155(10):4630-43. View

13.

Nosaka K, Maeda M, Tamiya S, Sakai T, Mitsuya H, Matsuoka M . Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia. Cancer Res. 2000; 60(4):1043-8. View

14.

Takasaki Y, Yamada Y, Sugahara K, Hayashi T, Dateki N, Harasawa H . Interruption of p16 gene expression in adult T-cell leukaemia/lymphoma: clinical correlation. Br J Haematol. 2003; 122(2):253-9. DOI: 10.1046/j.1365-2141.2003.04377.x. View

15.

Morrison M, Vijayasaradhi S, Engelstein D, Albino A, Houghton A . A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med. 1993; 177(4):1135-43. PMC: 2190962. DOI: 10.1084/jem.177.4.1135. View

16.

Yamada Y, Ohmoto Y, Hata T, Yamamura M, Murata K, Tsukasaki K . Features of the cytokines secreted by adult T cell leukemia (ATL) cells. Leuk Lymphoma. 1996; 21(5-6):443-7. DOI: 10.3109/10428199609093442. View

17.

Watanabe T . HTLV-1-associated diseases. Int J Hematol. 1997; 66(3):257-78. DOI: 10.1016/s0925-5710(97)00077-7. View

18.

Mattern T, Scholz W, Feller A, Flad H, Ulmer A . Expression of CD26 (dipeptidyl peptidase IV) on resting and activated human T-lymphocytes. Scand J Immunol. 1991; 33(6):737-48. DOI: 10.1111/j.1365-3083.1991.tb02548.x. View

19.

Ahmad S, Wang L, Ward P . Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating substance P in vivo. J Pharmacol Exp Ther. 1992; 260(3):1257-61. View

20.

Yasunaga J, Matsuoka M . Leukemogenesis of adult T-cell leukemia. Int J Hematol. 2003; 78(4):312-20. DOI: 10.1007/BF02983555. View