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Over‐expression of the dominant‐negative isoform of Ikaros confers resistance to dexamethasone‐induced and anti‐IgM‐induced apoptosis
Author(s) -
Sezaki Nobuo,
Ishimaru Fumihiko,
Takata Minoru,
Tabayashi Takayuki,
Nakase Koichi,
Kozuka Teruhiko,
Fujii Keiko,
Nakayama Hiroyuki,
Teshima Takanori,
Harada Mine,
Tanimoto Mitsune
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04263.x
Subject(s) - apoptosis , dexamethasone , downregulation and upregulation , gene isoform , cancer research , cell culture , transcription factor , biology , antibody , microbiology and biotechnology , immunology , medicine , gene , endocrinology , genetics
Summary. 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.