Clinical and oncologic implications in epigenetic down-regulation of CD26/ dipeptidyl peptidase IV in adult T-cell leukemia cells

• Published in: International journal of hematology Vol. 80; no. 3; pp. 254 - 260
• Main Authors: TSUJI, Tomohiro, SUGAHARA, Kazuyuki, TSURUDA, Kazuto, UEMURA, Akiko, HARASAWA, Hitomi, HASEGAWA, Hiroo, HAMAGUCHI, Yukio, TOMONAGA, Masao, YAMADA, Yasuaki, KAMIHIRA, Shimeru
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.10.2004; Springer Nature B.V
• Subjects: Biological and medical sciences; Biomarkers; Case-Control Studies; CpG Islands; Dipeptidyl Peptidase 4 - analysis; Dipeptidyl Peptidase 4 - genetics; DNA Methylation; Down-Regulation; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Leukemia-Lymphoma, Adult T-Cell - diagnosis; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Promoter Regions, Genetic; RNA - analysis; Dipeptidyl-peptidase IV; Adult T cell leukemia; Hematology; Enzyme; Retroviridae; Malignant hemopathy; CD26/DPPIV; Infection; Virus; Peptidases; Regulation(control); Adult T-cell leukemia; Lymphoproliferative syndrome; Viral disease; Down-regulation; Epigenetics; Hydrolases; HTLV-I virus
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1532/IJH97.04066

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.