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Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
2000 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 95, no 4, 1420-1426 p.Article in journal (Refereed) Published
Abstract [en]

Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor alpha (TNF-alpha), and CD40-ligation induced S-phase entry and mitosis in normal B cells and B-type chronic lymphocytic leukemia (B-CLL) cells. The viability of B-CLL cells stimulated by these protocols is high, and it has been hypothesized that the overexpression of Bcl-2 found in B-CLL protects the cells from apoptosis in vitro and in vivo. In this study, we have analyzed the response of cells derived from 12 samples of patients with B-CLL to recombinant human Trx in spontaneous apoptosis, with special reference to the Bcl-2 expression. Long-term cultures of B-CLL clones showed significantly higher viability when supplemented with human Trx (P =.031), also exemplified with clones surviving more than 2 months. Short-term cultures of B-CLL cells exposed to 1 microg/mL of Trx for 1, 5, or 12 days maintained expression or delayed down-regulation of Bcl-2 compared with control cultures containing RPMI 1640 medium and 10% fetal calf serum only (P =.032,. 002,.026, respectively). All B-CLL cells expressed constitutive Trx at varying but low levels, in contrast to adult T-cell leukemias, which overexpress Trx, as previously reported. We found that Trx added to B-CLL cells increased in a dose-dependent fashion the release of TNF-alpha, which has been suggested to be an autocrine growth factor for these cells. In conclusion, we have found that human recombinant Trx induced TNF-alpha secretion, maintained Bcl-2, and reduced apoptosis in B-CLL cells.

Place, publisher, year, edition, pages
2000. Vol. 95, no 4, 1420-1426 p.
Keyword [en]
Adult, Aged, Aged; 80 and over, Apoptosis/drug effects, Cell Cycle/drug effects, Cell Survival/*drug effects, Female, Gene Expression Regulation; Neoplastic, Humans, Interleukin-1/analysis, Interleukin-6/analysis, Kinetics, Leukemia; B-Cell; Chronic/immunology/*pathology, Male, Middle Aged, Proto-Oncogene Proteins c-bcl-2/genetics, Recombinant Proteins/pharmacology, Research Support; Non-U.S. Gov't, Thioredoxin/*pharmacology, Time Factors, Tumor Cells; Cultured, Tumor Necrosis Factor-alpha/analysis
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-69631PubMedID: 10666220OAI: oai:DiVA.org:uu-69631DiVA: diva2:97542
Available from: 2005-04-07 Created: 2005-04-07 Last updated: 2013-11-05Bibliographically approved

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Söderberg, OlaNilsson, Kenneth
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