Premium
Adult T‐cell leukemia cells over‐express the multidrug‐resistance‐protein (MRP) and lung‐resistance‐protein (LRP) genes
Author(s) -
Ikeda Koki,
Oka, Mikio,
Yamada Yasuaki,
Soda Hiroshi,
Fukuda Minoru,
Kinoshita Akitoshi,
Tsukamoto Kazuhiro,
Noguchi Yuji,
Isomoto Hajime,
Takeshima Fuminao,
Murase Kunihiko,
Kamihira Shimeru,
Tomonaga Masao,
Kohno Shigeru
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990812)82:4<599::aid-ijc21>3.0.co;2-r
Subject(s) - peripheral blood mononuclear cell , t cell leukemia , biology , leukemia , immunology , multiple drug resistance , cancer research , medicine , in vitro , drug resistance , biochemistry , microbiology and biotechnology
Adult T‐cell leukemia (ATL) is a T‐cell malignancy caused by human T‐cell‐leukemia‐virus‐I (HTLV‐I) infection. ATL comprises 4 clinical forms: acute, chronic, smoldering and lymphoma types. ATL is usually resistant to conventional chemotherapy and has a relatively poor prognosis; however, the resistance mechanisms remain undetermined. To explore the multidrug‐resistance (MDR) mechanisms of ATL, we examined the expression and functional activity of MDR‐related genes in peripheral‐blood mononuclear cells (PBMC) from ATL patients by semi‐quantitative RT‐PCR and FACScan with calcein‐AM. PBMC from ATL patients expressed similar or higher levels of MRP, LRP and cMOAT mRNAs, as compared with normal PBMC. In normal controls and ATL patients, MDR 1 mRNA expression was undetectable in this study. PBMC from acute and chronic ATL patients expressed significantly higher levels of MRP and LRP mRNA than did normal PBMC ( p < 0.01 and p < 0.05 respectively). In chronic ATL, positive correlations were apparent between levels of MRP and LRP mRNA expression (r = 0.759, p = 0.018), and between each mRNA level and the absolute number of abnormal lymphocytes in peripheral blood. Probenecid, an inhibitor of the MRP pump, significantly increased the accumulation of calcein in PBMC from 3 chronic ATL patients. Our findings suggest that the MRP and LRP genes in ATL are often activated by HTLV‐I infection and may confer MDR of ATL cells in vivo. Combined chemotherapy with inhibitors of these MDR genes may be promising in the treatment of ATL. Int. J. Cancer 82:599–604, 1999. © 1999 Wiley‐Liss, Inc.