Alpha interferon therapy for haematological malignancies: correlation between in vivo induction of the 2',5'oligoadenylate system and clinical response.
2',5'oligoadenylate (2-5A) synthetase mRNA and enzyme levels have been studied in peripheral blood mononuclear cells from 12 patients with chronic granulocytic leukaemia (CGL), 14 with essential thrombocythaemia (ET) and nine with chronic lymphocytic leukaemia (CLL), undergoing therapy with alpha interferon (alpha IFN). 2-5A synthetase mRNA was assayed by hybridization using the dot-blot technique and the enzyme activity was measured biochemically. A statistically significant difference was observed (P less than 0.05) between the degree of in vivo induction of mRNA by IFN alpha in the total patients between the good and intermediate responders and the poor responders. There was a similar pattern in each of the CGL, ET and CLL groups although this only reached statistical significance in the CGL group. In vitro induction of either mRNA or of enzyme activity, however, did not show a difference between the responders and poor responders in any of the patient groups. Our findings are consistent with the concept that 2-5A has an important role in the anti-tumour activity of alpha IFN and suggest that measurement of in vivo induction of 2-5A synthetase mRNA may be useful in predicting clinical response. In vitro studies, on the other hand, do not provide a reliable predictor of clinical response.
de Mel
W C
WC
Department of Haematology, Royal Free Hospital School of Medicine, London.
Hoffbrand
A V
AV
Giles
F J
FJ
Goldstone
A H
AH
Mehta
A B
AB
Ganeshaguru
K
K
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000201:enzymology / Q000628:therapy*
D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase