Recombinant human interferon alpha-2 and juvenile chronic myelogenous leukemia: cell receptor binding, enzymatic induction, and growth suppression in vitro.
Recombinant human leukocyte interferon (HuIFN alpha 2) was studied to determine its potential as a therapeutic agent for the lethal monocytic malignancy of infancy, juvenile chronic myelogenous leukemia (JCML). In sharp contrast to cell cultures of normal marrow, specimens from two patients with JCML yielded an excessive and rapid proliferation of monocyte-macrophage elements without growth factor in clonogenic assay and in liquid culture. Using IFN alpha 2 labeled with 125I, the characteristics of IFN binding to cultured JCML monocyte-macrophages and their receptor site numbers were determined. IFN binding to cells from both patients disclosed two components: a high-affinity of 120 and 430 sites/cell, and a lower affinity of 1230 and 2500 sites/cell, respectively. In control studies, normal blood mononuclear cells or tonsillar B-lymphocytes displayed only a high-affinity component. Brief exposure of JCML cells to IFN alpha 2 in vitro resulted in a sharp increase in the IFN-induced enzyme 2-5A synthetase, indicating the ability of JCML cells to respond metabolically. Dose-response studies performed in a clonogenic assay showed a dose-dependent growth inhibition of JCML monocyte-macrophage colonies using IFN alpha 2 at concentrations of 10(2)-10(5) U/ml. These studies provide new information on the biological characteristics of JCML malignant cells, and suggest that IFN may be useful for treatment of this disorder.
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D011955:Receptors, Drug / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use*
D011955:Receptors, Drug; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase