Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2'-5')oligo (A) synthetase in tumor cells from sensitive and resistant patients.
IFN-alpha induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN-alpha receptors which are down-regulated upon therapy. We show here that the activity of 2-5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12-24 h after the first IFN dose. This in-vivo enzyme induction paralleled the kinetics of receptor down-regulation. In one patient who was unresponsive to IFN-alpha treatment neither expression of IFN-alpha receptor nor change in 2-5 A synthetase were expressed and modulated as in sensitive patients. In-vitro treatment of hairy cells with recombinant interferons showed that IFN-beta 1 was able to induce this enzyme to the same extent than IFN-alpha 2, whereas IFN-gamma was inactive despite the presence of specific IFN-gamma receptors. Our results indicate that IFN-alpha can exert its therapeutic effects by acting directly on the hairy cells through interaction with surface membrane receptors. Induction of 2-5 A synthetase can be one of the steps involved in this action. However, both mechanisms, as well as receptor down-regulation are not sufficient to explain the responsiveness of hairy cell leukemia to IFN-alpha.
Billard
C
C
Unité de recherches sur les interférons, INSERM U 196, Paris, France.
Ferbus
D
D
Sigaux
F
F
Castaigne
S
S
Degos
L
L
Flandrin
G
G
Falcoff
E
E
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D015088:2',5'-Oligoadenylate Synthetase