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: K Nakase, F Ishimaru, N Avitahl, H Dansako, K Matsuo, K Fujii, N Sezaki, H Nakayama, T Yano, S Fukuda, K Imajoh, M Takeuchi, A Miyata, M Hara, M Yasukawa, I Takahashi, H Taguchi, K Matsue, S Nakao, Y Niho, K Takenaka, K Shinagawa, K Ikeda, K Niiya, M Harada
• Journal: Cancer research (Cancer Res) Vol. 60 Issue 15 Pg. 4062-5 (Aug 01 2000) ISSN: 0008-5472 [Print] United States
• PMID: 10945610 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• IKZF1 protein, human
• Protein Isoforms
• Transcription Factors
• Ikaros Transcription Factor

Topics

• Adolescent
• Adult
• Alternative Splicing
• Bone Marrow Cells (metabolism)
• Burkitt Lymphoma (genetics, metabolism)
• DNA-Binding Proteins
• Female
• Gene Expression
• Genes, Dominant (genetics)
• Humans
• Ikaros Transcription Factor
• Male
• Middle Aged
• Protein Isoforms (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors (biosynthesis, genetics)
• Zinc Fingers (genetics)