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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Nakase K,Ishimaru F,Avitahl N,Dansako H,Matsuo K,Fujii K,Sezaki N,Nakayama H,Yano T,Fukuda S,Imajoh K,Takeuchi M,Miyata A,Hara M,Yasukawa M,Takahashi I,Taguchi H,Matsue K,Nakao S,Niho Y,Takenaka K,Shinagawa K,

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

4062-5

issue

15

eissn

0008-5472

issn

1538-7445

journal_volume

60

pub_type

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