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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vedantham, S. Articles by Golomb, H. M. Search for Related Content PubMed PubMed Citation Articles by Vedantham, S. Articles by Golomb, H. M.

Mechanism of Interferon Action in Hairy Cell Leukemia: A Model of Effective Cancer Biotherapy¹

Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois 60637

Hairy cell leukemia (HCL) is one of the few malignancies for which -interferon (IFN) 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-treated HCL patients is dependent upon enhancement of host defenses or upon direct actions of IFN 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 in HCL, the purpose being to determine which proposed mechanisms of IFN action are indeed effective in vivo. From our analysis, it appears that the beneficial effects of IFN upon immune function are important in decreasing the frequency of infections complications of HCL but that these effects are probably not responsible for hairy cell elimination and cannot therefore account for major responses to IFN therapy. We conclude that the primary mechanism of action of IFN 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 in HCL to the biotherapy of cancer are discussed.

¹ This work was supported in part by the Hematologic Research Foundation and the Hairy Cell Leukemia Research Foundation.

² To whom requests for reprints should be addressed, at 729 East Third St., Hinsdale, IL 60521.

Received 10/31/91. Accepted 12/17/91.

This article has been cited by other articles:

				C. Muhr, O. Gudjonsson, A. Lilja, M. Hartman, Z.-J. Zhang, and B. Langstrom Meningioma Treated with Interferon-{alpha}, Evaluated with [11C]-L-Methionine Positron Emission Tomography Clin. Cancer Res., August 1, 2001; 7(8): 2269 - 2276. [Abstract] [Full Text] [PDF]

				V. R. Agarwal, E. D. Bischoff, T. Hermann, and W. W. Lamph Induction of Adipocyte-specific Gene Expression Is Correlated with Mammary Tumor Regression by the Retinoid X Receptor-Ligand LGD1069 (Targretin) Cancer Res., November 1, 2000; 60(21): 6033 - 6038. [Abstract] [Full Text]

				M. Shehata, J. D. Schwarzmeier, S. T. Nguyen, M. Hilgarth, R. Berger, R. Hubmann, S. Kickmaier, and T. Decker Reconstitution of Endogenous Interferon {{alpha}} by Recombinant Interferon in Hairy Cell Leukemia Cancer Res., October 1, 2000; 60(19): 5420 - 5426. [Abstract] [Full Text]

				S. Wadler and E. L. Schwartz New Advances in Interferon Therapy of Cancer Oncologist, August 1, 1997; 2(4): 254 - 267. [Abstract] [Full Text] [PDF]