Hairy cell leukemia is a lymphoproliferative disorder with invasion of the bone marrow and spleen characterized clinically by sytemic cytopenias. We and others have shown that over 90% of these patients show complete or partial responses to therapy with interferon-Alpha (IFN). Although the majoritiy of these patients have normal numbers of circulating natural killer cells (NK) prior to therapy, they all exhibit a marked depression in NK cytolytic activity. In most patients responding clinically to the IFN Therapy, this defect in NK function was corrected to near normal values. This occurred concomittently with the loss of circulating hairy cells and normalization of peripheral blood counts. The research is focused at determining the nature of this immune cell defect, the role of the circulating hairy cell and how IFN might modulate this phenomenon. We will evaluate NK cell function in patients before and during therapy. This will include detemrination of the frequency and efficiency of isolated NK cells, (leu 11+) at the single cell level. To determine whether cells (pre-NK) from this population can be recruited to be functionally active NK cells, we will examine their responsiveness to IFN in vitro. We will also establish B-cell growth factor (BCGF) dependent cell lines form hairy cell leukemia patients. These will be used to determine a) if hairy cells can modulate or suppress normal NK activity, b) if hairy cells can serve as susceptible targets of NK cytotoxicity, and c) the influence of IFN on these parameters. In addition, we will evaluate direct effects of IFN on the kinetics of hairy cell growth in vitro, expression of cellular protooncogenes, and changes in markers of cell differentiation. These studies may provide us with new insights regarding the mechanisms of action of IFN in this responsive disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043212-02
Application #
3185273
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1986-09-30
Project End
1987-08-31
Budget Start
1987-07-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Bonavida, B (1992) TNF as immunomodulatory agent. Immunol Ser 56:315-29