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Interferon-stimulated Genes in Interferon-sensitive and -resistant Chronic Myelogenous Leukemia Patients

Departments of Clinical Immunology and Biological Therapy [M. T., K. T-W., M. W., J. U. G., R. K.], Immunology [Y. C.], and Hematology [H. K.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

-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 -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 -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 -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 -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.

¹ To whom requests for reprints should be addressed, at Department of Clinical Immunology and Biological Therapy, Box 41, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 5/ 8/91. Accepted 12/13/91.

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