Alpha-interferon receptors in malignant B-cells from patients with chronic lymphocytic leukemia: relation to induction of 2'-5'-oligoadenylate synthetase and blast transformation.
alpha-Interferon (IFN-alpha) induces blast transformation of malignant B-cells from approximately 65% of chronic lymphocytic leukemia patients. We have shown previously that induction of blast transformation correlates with induction of 2'-5'-oligoadenylate synthetase. In this paper we address the question of whether low responsiveness to IFN-alpha is associated with a reduced expression of the IFN receptor. IFN-alpha receptor expression was studied by the binding of radioiodinated IFN-alpha to peripheral blood malignant B-cells from 20 chronic lymphocytic leukemia patients and to blood cells from 5 healthy donors. Chronic lymphocytic leukemia cells from all 20 patients displayed high affinity IFN-alpha receptors [mean Kd, 62 +/- 9 (SE) pM] ranging between 110 and 850 binding sites/cell [mean, 416 +/- 51]. Nonmalignant mononuclear blood cells showed similar binding data (411 +/- 105 binding sites/cell; Kd 66 +/- 20 pM). Receptor expression did not correlate with the degree of blast transformation or with induction of 2'-5'-oligoadenylate synthetase. We conclude that the deficiency of IFN sensitivity is localized somewhere between signal transduction from the receptor and induction of 2'-5'-oligoadenylate synthetase.
Ostlund
L
L
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Grandér
D
D
Juliusson
G
G
Robèrt
K H
KH
Lundgren
E
E
Einhorn
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D001752:Blast Crisis / Q000276:immunology*; D002478:Cells, Cultured; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon
D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D015088:2',5'-Oligoadenylate Synthetase