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

a-Interferon induces hematological and cytogenetic remissions in some individuals with newly diagnosed Philadelphia-positive chronic myelogenous leukemia. However, interferon-resistant disease occurs in a con sistent patient subset (primary resistance) and develops during therapy in additional patients (secondary resistance). Several o-interferon-inducible genes have been characterized. In interferon-resistant cell line var iants, 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 a-interferon therapy. Twenty-seven chronic myelogenous leukemia patients (ten interferon sensitive patients, 17 interferon-resistant patients) were studied. Periph eral 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 a-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 a-interferon in chronic myelogenous leukemia patients. Other mechanisms such as posttranslational modification, leading to defects in the ISG correspond ing proteins, may play a role in the development of resistance.