title: Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia.
abstract: Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.
authors.affiliation: Department of Medicine, University of Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakase
authors.forename: F
authors.initials: F
authors.lastname: Ishimaru
authors.forename: N
authors.initials: N
authors.lastname: Avitahl
authors.forename: H
authors.initials: H
authors.lastname: Dansako
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: N
authors.initials: N
authors.lastname: Sezaki
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Imajoh
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: A
authors.initials: A
authors.lastname: Miyata
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Yasukawa
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Taguchi
authors.forename: K
authors.initials: K
authors.lastname: Matsue
authors.forename: S
authors.initials: S
authors.lastname: Nakao
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
authors.forename: K
authors.initials: K
authors.lastname: Takenaka
authors.forename: K
authors.initials: K
authors.lastname: Shinagawa
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Niiya
authors.forename: M
authors.initials: M
authors.lastname: Harada
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001854:Bone Marrow Cells / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors; D051740:Ikaros Transcription Factor