Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia.
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.
Nakase
K
K
Department of Medicine, University of Okayama, Japan.
Ishimaru
F
F
Avitahl
N
N
Dansako
H
H
Matsuo
K
K
Fujii
K
K
Sezaki
N
N
Nakayama
H
H
Yano
T
T
Fukuda
S
S
Imajoh
K
K
Takeuchi
M
M
Miyata
A
A
Hara
M
M
Yasukawa
M
M
Takahashi
I
I
Taguchi
H
H
Matsue
K
K
Nakao
S
S
Niho
Y
Y
Takenaka
K
K
Shinagawa
K
K
Ikeda
K
K
Niiya
K
K
Harada
M
M
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*
D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors; D051740:Ikaros Transcription Factor