Interferon-stimulated genes in interferon-sensitive and -resistant chronic myelogenous leukemia patients. Cancer Res 1992 Mar 01;52(5):1087-90
Date
03/01/1992Pubmed ID
1737366Scopus ID
2-s2.0-0026516533 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
alpha-Interferon induces hematological and cytogenetic remissions in some individuals with newly diagnosed Philadelphia-positive chronic myelogenous leukemia. However, interferon-resistant disease occurs in a consistent patient subset (primary resistance) and develops during therapy in additional patients (secondary resistance). Several alpha-interferon-inducible genes have been characterized. In interferon-resistant cell line variants, defects in these genes have been implicated in the mechanisms mediating resistance. We have, therefore, evaluated mRNA expression of four interferon-stimulated genes (ISGs) following alpha-interferon therapy. Twenty-seven chronic myelogenous leukemia patients (ten interferon-sensitive patients, 17 interferon-resistant patients) were studied. Peripheral blood samples were collected prior to and 1 to 7 days after starting interferon therapy and analyzed for the expression of 2'-5' oligoadenylate synthetase, ISG-15, ISG-54, and 6-16 transcripts. Following therapy with alpha-interferon, 2'-5' oligoadenylate synthetase, ISG-54, and 6-16 transcripts were discerned in all patients regardless of their response to interferon. The ISG-15 message was detected in eight of nine interferon-sensitive and in 15 of 16 interferon-resistant patients, as well. Overall, no consistent defect in the ISG system could be identified. Therefore, lack of induction of these genes cannot explain resistance to alpha-interferon in chronic myelogenous leukemia patients. Other mechanisms such as posttranslational modification, leading to defects in the ISG corresponding proteins, may play a role in the development of resistance.
Author List
Talpaz M, Chernajovsky Y, Troutman-Worden K, Wetzler M, Kantarjian H, Gutterman JU, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
2',5'-Oligoadenylate SynthetaseBlotting, Northern
Drug Resistance
Gene Expression
Humans
Interferon-alpha
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
RNA, Messenger
RNA, Neoplasm