Identification of a Complex Formed Between Nuclear Proteins and the Transcriptional Enhancer of Interferon-Inducible Genes That Is Present in the Peripheral Blood Myeloid Cells of CML but Not Normal Individuals

Interferon-α (IFN-α) induces cytogenetic remissions in 20% of chronic myelogenous leukemia (CML) patients. To clarify the mechanisms through which this antiproliferative action of IFN is mediated in the CML cell, a modification of the mobility-shift assay was used to follow the formation of complexes between nuclear proteins and IFN-inducible transcriptional enhancers involved in mediating the cellular effects of IFN-α. These studies identified a complex that was present in the myeloid cells of 18/24 (75%) of chronic-phase CML patients tested whose cells contained 100% Philadelphia chromosome positive (Ph⁺) cells, while the proteins of none of the samples tested from normal peripheral blood samples and only 22% (2/9) of the CML patients in an IFN-induced major cytogenetic remission (less than 30% Ph⁺ cells) contained these complexes. These studies suggest that the mobility-shift assay detects changes in the CML myeloid cell that distinguish it from the normal myeloid cell.