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: Nobuo Sezaki, Fumihiko Ishimaru, Minoru Takata, Takayuki Tabayashi, Koichi Nakase, Teruhiko Kozuka, Keiko Fujii, Hiroyuki Nakayama, Takanori Teshima, Mine Harada, Mitsune Tanimoto
• Journal: British journal of haematology (Br J Haematol) Vol. 121 Issue 1 Pg. 165-9 (Apr 2003) ISSN: 0007-1048 [Print] England
• PMID: 12670348 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• DNA-Binding Proteins
• Glucocorticoids
• IKZF1 protein, human
• Immunoglobulin M
• Protein Isoforms
• Transcription Factors
• Ikaros Transcription Factor
• Dexamethasone

Topics

• Analysis of Variance
• Antibodies, Anti-Idiotypic (pharmacology)
• Apoptosis
• B-Lymphocytes (metabolism, pathology)
• Burkitt Lymphoma (immunology)
• Cell Line
• DNA-Binding Proteins
• Dexamethasone (pharmacology)
• Flow Cytometry
• Gene Expression
• Glucocorticoids (pharmacology)
• Humans
• Ikaros Transcription Factor
• Immunoblotting
• Immunoglobulin M (immunology)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (immunology)
• Protein Isoforms (metabolism)
• Transcription Factors (metabolism)