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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Reiter, Z. Articles by Taylor, M. W. Search for Related Content PubMed PubMed Citation Articles by Reiter, Z. Articles by Taylor, M. W. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Combination treatment of 2-chlorodeoxyadenosine and type I interferon on hairy cell leukemia-like cells: cytotoxic effect and MHC- unrestricted killer cell regulation Z Reiter, S Tomson, ON Ozes and MW Taylor Division of Morphological Sciences, Faculty of Medicine, Technion, Haifa, Israel. Hairy cell leukemia (HCL) is a lymphoproliferative disorder of B lymphocytes. Interferons (IFNs), especially of the alpha (alpha) subtype, have shown a significant antitumor effect in HCL patients. However, the therapeutic effect of IFN-alpha is still rather limited. The purine analogue 2-chlorodeoxy-adenosine (2-CdA) was reported recently to be an effective agent in the treatment of HCL. In the present study, we find that the HCL cell lines HS-1 and HS-2 as well as Eskol and its IFN-resistant clone (IREs-4) are sensitive to the cytotoxic activity of 2-CdA. Combination treatment of IFN-Con1 and 2- CdA results in a synergistic effect at low doses but an additive inhibitory effect at higher concentrations. IREs-4 cells responded only to 2-CdA treatment. All the HCL cell lines are resistant to natural killer (NK) cell-mediated cytotoxicity (CMC) but are relatively sensitive to IFN-Con1-primed or interleukin-2 (IL-2)-primed NK-CMC activities. No inhibition in killing ability was measured when only the effector cells (NK) were treated with 2-CdA. Pretreatment of the HCL target cells with 2-CdA increases their susceptibility to NK-CMC. Pretreatment with IFN-Con1 can reduce the susceptibility of target cells to NK-CMC in HS-1, HS-2, and Eskol cells but not in the IFN- resistant clone IREs-4. 2-CdA abolished this IFN-induced protection against NK-CMC. Normal fibroblasts only responded to treatment with relatively high doses of 2-CdA, and only a moderate additive cell growth inhibitory effect was seen in combination of 2-CdA with IFN- Con1. Only high doses of 2-CdA increased the susceptibility of fibroblast culture to NK-CMC. Thus, combination of IFN-Con1 and 2-CdA results in an in vitro enhancement of the direct antiproliferative/cytotoxic activity of each treatment alone and increases the efficacy of the NK activity against the HCL cell lines. Volume 81, Issue 7, pp. 1699-1708, 04/01/1993 Copyright © 1993 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Markasz, G. Stuber, B. Vanherberghen, E. Flaberg, E. Olah, E. Carbone, S. Eksborg, E. Klein, H. Skribek, and L. Szekely Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells Mol. Cancer Ther., February 1, 2007; 6(2): 644 - 654. [Abstract] [Full Text] [PDF] S. Hortelano and L. Bosca 6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes Mol. Pharmacol., March 1, 1997; 51(3): 414 - 421. [Abstract] [Full Text] [PDF]

	Copyright © 1993 by American Society of Hematology         Online ISSN: 1528-0020