title: Over-expression of the dominant-negative isoform of Ikaros confers resistance to dexamethasone-induced and anti-IgM-induced apoptosis.
abstract: In previous studies, we demonstrated an over-expression of the dominant-negative isoform of the transcription factor Ikaros, Ik-6, in patients with B-cell malignancies, including blast crisis of chronic myelogenous leukaemia and acute lymphoblastic leukaemia. To investigate the consequence of over-expression of Ik-6 in B cells, we constructed Ik-6 transfectants of the FDH-1 and Ramos cell lines. FDH-1, which was established from a patient with early pre-B acute lymphoblastic leukaemia, undergoes apoptosis with dexamethasone treatment, whereas Ramos undergoes apoptosis following anti-IgM antibody treatment. Compared with the wild type, the over-expression of Ik-6 rendered the FDH-1 and Ramos transfectants resistant to dexamethasone-induced and anti-IgM-induced apoptosis respectively. An immunoblotting study demonstrated bcl-2 upregulation in anti-IgM-induced Ramos Ik-6 transfectants, but not in FDH-1 Ik-6 transfectants. Further investigations of the mechanism of leukaemogenesis associated with the over-expression of Ik-6 are warranted.
authors.affiliation: Department of Medicine, University of Okayama, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sezaki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishimaru
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tabayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakase
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kozuka
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000704:Analysis of Variance; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002051:Burkitt Lymphoma / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D051740:Ikaros Transcription Factor; D015151:Immunoblotting; D007075:Immunoglobulin M / Q000276:immunology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; C497239:IKZF1 protein, human; D007075:Immunoglobulin M; D020033:Protein Isoforms; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; D003907:Dexamethasone