Document Detail

Mechanism of interferon action in hairy cell leukemia: a model of effective cancer biotherapy.
MedLine Citation:
PMID:  1737364     Owner:  NLM     Status:  MEDLINE    
Hairy cell leukemia (HCL) is one of the few malignancies for which alpha-interferon (IFN alpha) is considered effective first-line therapy. However, the mechanisms of action of this agent in vivo have been the subject of much debate; in particular, the issue of whether clinical improvement in IFN-alpha-treated HCL patients is dependent upon enhancement of host defenses or upon direct actions of IFN alpha upon the hairy cell remains unresolved. In this review, we examine the evidence supporting both lines of argument and synthesize this information within the framework of clinical studies of IFN alpha in HCL, the purpose being to determine which proposed mechanisms of IFN alpha action are indeed effective in vivo. From our analysis, it appears that the beneficial effects of IFN alpha upon immune function are important in decreasing the frequency of infectious complications of HCL but that these effects are probably not responsible for hairy cell elimination and cannot therefore account for major responses to IFN alpha therapy. We conclude that the primary mechanism of action of IFN alpha in HCL involves the induction of hairy cell differentiation towards a stage less responsive to growth factor stimulation, the primary consequence being proliferative inhibition. These effects may mimic events that occur during normal lymphocyte development, suggesting that the benefits of biotherapeutic agents might best be harnessed via studies of the effects of multiple and sequential biological response modifiers upon the growth and differentiation patterns of normal and malignant cells. Hairy cell leukemia could thus serve as an excellent model in which to investigate combined cancer biotherapy; the implications of our present understanding of IFN alpha in HCL to the biotherapy of cancer are discussed.
S Vedantham; H Gamliel; H M Golomb
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cancer research     Volume:  52     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1992 Mar 
Date Detail:
Created Date:  1992-03-18     Completed Date:  1992-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1056-66     Citation Subset:  IM    
Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Illinois 60637.
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MeSH Terms
Cell Differentiation / drug effects
Gene Expression / drug effects
Growth Substances / pharmacology
HLA Antigens / immunology
Hematopoietic Stem Cells / drug effects
Immunity / drug effects
Interferon-alpha / pharmacology,  therapeutic use*
Killer Cells, Natural / drug effects
Leukemia, Hairy Cell / immunology,  pathology,  therapy*
Oncogenes / drug effects
Reg. No./Substance:
0/Growth Substances; 0/HLA Antigens; 0/Interferon-alpha

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