Abstract |
Chemotherapy for adult T-cell leukemia (ATL) has been reported to fail to induce complete remission because of drug resistance in most patients. We have examined the expression of an ATL-derived factor (ADF)/ thioredoxin in relation to resistance to adriamycin (ADM) in various T-cell leukemia cell lines including ATL cell lines. Immunoblot analysis demonstrated that ATL cell lines expressed ADF/ thioredoxin at levels 2.8 to 12 times those of other T-cell acute lymphocytic leukemia ( T-ALL) cell lines, and that ATL cell lines were 2 to 15 times more resistant to ADM than other T-ALL cell lines. Therefore, we established ADM-resistant cell lines from three different ATL cell lines, and examined the correlation between ADM resistance and expression of ADF/ thioredoxin. ADM-resistant ATL cell lines were also found to be resistant to other drugs such as cisplatin and etoposide, and they expressed ADF/ thioredoxin at levels 5 to 10 times those of parent ATL cell lines. Diamide and sodium selenite, which have been reported to inhibit ADF/ thioredoxin, restored the sensitivity to ADM in ATL and ADM-resistant ATL cell lines. The MDR-1 gene product, a membrane P-glycoprotein (Pgp), was not expressed on ATL cell lines or ADM-resistant ATL cell lines. Topoisomerase II and glutathione peroxidase activities in T-cell leukemia cell lines were not correlated with ADM resistance. These results suggest that ADF/ thioredoxin may play an important role in the drug resistance of ATL cells to ADM.
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Authors | J Wang, M Kobayashi, K Sakurada, M Imamura, T Moriuchi, M Hosokawa |
Journal | Blood
(Blood)
Vol. 89
Issue 7
Pg. 2480-7
(Apr 01 1997)
ISSN: 0006-4971 [Print] United States |
PMID | 9116292
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Cytokines
- Neoplasm Proteins
- adult T cell leukemia-derived factor
- Diamide
- Thioredoxins
- Doxorubicin
- Glutathione Peroxidase
- DNA Topoisomerases, Type II
- Sodium Selenite
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(biosynthesis)
- Cytokines
(physiology)
- DNA Topoisomerases, Type II
(analysis)
- Diamide
(pharmacology)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
- Glutathione Peroxidase
(analysis)
- Leukemia, T-Cell
(drug therapy, metabolism)
- Neoplasm Proteins
(physiology)
- Sodium Selenite
(pharmacology)
- Thioredoxins
(metabolism)
- Tumor Cells, Cultured
(drug effects)
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