title: 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.
abstract: Interferon-alpha (INF-alpha) 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-alpha. 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.
authors.affiliation: Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: D C
authors.initials: DC
authors.lastname: Seong
authors.forename: K
authors.initials: K
authors.lastname: Gottlieb
authors.forename: S P
authors.initials: SP
authors.lastname: Suh
authors.forename: S
authors.initials: S
authors.lastname: Sims
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: A
authors.initials: A
authors.lastname: Deisseroth
mesh_terms: D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000628:therapy*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D012016:Reference Values; D012074:Remission Induction / Q000379:methods; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
chemical_list: D016898:Interferon-alpha; D009687:Nuclear Proteins