Document Detail

Combination treatment of 2-chlorodeoxyadenosine and type I interferon on hairy cell leukemia-like cells: cytotoxic effect and MHC-unrestricted killer cell regulation.
MedLine Citation:
PMID:  8096405     Owner:  NLM     Status:  MEDLINE    
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.
Z Reiter; S Tomson; O N Ozes; M W Taylor
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  81     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1993 Apr 
Date Detail:
Created Date:  1993-05-04     Completed Date:  1993-05-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1699-708     Citation Subset:  AIM; IM    
Division of Morphological Sciences, Faculty of Medicine, Technion, Haifa, Israel.
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MeSH Terms
Cell Division / drug effects
Cladribine / pharmacology*
Cytotoxicity, Immunologic / drug effects
Drug Synergism
Drug Therapy, Combination
Immunity, Cellular / drug effects
Interferon Type I, Recombinant / pharmacology*
Interleukin-2 / pharmacology
Killer Cells, Natural / drug effects*,  immunology
Leukemia, Hairy Cell / immunology,  pathology*,  therapy
Lymphocyte Activation / drug effects
Major Histocompatibility Complex / immunology*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Interferon Type I, Recombinant; 0/Interleukin-2; 118390-30-0/interferon alfacon-1; 4291-63-8/Cladribine

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