Possible roles of an adult T-cell leukemia (ATL)-derived factor/thioredoxin in the drug resistance of ATL to adriamycin.

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.

• 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)

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

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)