Effect of recombinant alpha-interferon on the expression of the bcr-abl fusion gene in human chronic myelogenous human leukemia cell lines.
Recent investigations have shown a therapeutic and cytogenetic response in chronic myelogenous leukemia (CML) patients treated with recombinant alpha 2-interferon (IFN alpha 2). Philadelphia chromosome-positive (and many Ph1-negative) chronic myelogenous leukemia cells transcribe a novel bcr-abl fusion mRNA which may confer a growth advantage upon these cells. We investigated the effect of IFN alpha 2 on the levels of bcr-abl transcript expression in three Ph1-positive CML cell lines, EM2, KCL22, and K562. Although IFN alpha 2 inhibited cell proliferation in all three CML cell lines, IFN alpha 2 had no effect on the level of bcr-abl mRNA expression in any of the CML cell lines. In contrast, IFN alpha 2 increased the expression of class I HLA gene products. We conclude that while the bcr-abl fusion gene and its transcript undoubtedly play key roles in the pathogenesis of CML, the antiproliferative effect of IFN alpha 2 in CML cell lines relies upon genetic mechanisms other than modulation of bcr-abl expression.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects*; D005805:Genes, MHC Class I / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000235:genetics*; D010677:Philadelphia Chromosome; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins