Over-expression of the dominant-negative isoform of Ikaros confers resistance to dexamethasone-induced and anti-IgM-induced apoptosis.
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.
Sezaki
Nobuo
N
Department of Medicine, University of Okayama, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Ishimaru
Fumihiko
F
Takata
Minoru
M
Tabayashi
Takayuki
T
Nakase
Koichi
K
Kozuka
Teruhiko
T
Fujii
Keiko
K
Nakayama
Hiroyuki
H
Teshima
Takanori
T
Harada
Mine
M
Tanimoto
Mitsune
M
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*
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