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-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.
Seong
D C
DC
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Gottlieb
K
K
Suh
S P
SP
Sims
S
S
Talpaz
M
M
Kantarjian
H
H
Deisseroth
A
A
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
D016898:Interferon-alpha; D009687:Nuclear Proteins