Interferon alpha-2 for hairy cell leukemia: evidence for induction of RNA synthesis in hairy cells and failure to correlate enhancement of natural Killer cells with elimination of hairy cells

The effect of human recombinant interferon α2 (IFNα2) on hairy cells obtained from 16 patients was evaluated. All patients promptly responded to induction of remission with 2 times 106 U/m2 interferon α2b, three times a week, sc. In order to achieve a more detailed insight into the mode of action of interferon in this disease, we determined the influence of IFNα2 on the incorporation of radiolabeled thymidine and uridine into hairy cells. While both 3H-thymidine and 3H-uridine incorporation were unaffected by IFNα2 in a 3-hour incubation period, a significant increase in uridine incorporation into hairy cells, but not CLL cells, was observed after 24 h. Cell surface marker analysis performed with monoclonal antibodies did not reveal a quantitative alteration of the immunophenotype of hairy cells in vitro. In addition, natural killer cells, assessed by monoclonal antibodies and a cytotoxicity assay against K 562 cells, were found to be decreased in 9 out of 10 patients prior to therapy. Although IFNα2 could stimulate natural killer cells in vivo, we did not find a consistent correlation between the activation of these cells and the response to therapy. We conclude, therefore, that NK cells play no major role in the regression of hairy cells. Furthermore, IFNα2 does not alter antigenic determinants in vitro, but leads to an enhanced incorporation of 3H-uridine into hairy cells in vitro, thus indicating a possible role for the induction of RNA synthesis in vivo.