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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-08, Vol.60 (15), p.4062-4065
Main Authors: NAKASE, K, ISHIMARU, F, IMAJOH, K, TAKEUCHI, M, MIYATA, A, HARA, M, YASUKAWA, M, TAKAHASHI, I, TAGUCHI, H, MATSUE, K, NAKAO, S, NIHO, Y, AVITAHL, N, TAKENAKA, K, SHINAGAWA, K, IKEDA, K, NIIYA, K, HARADA, M, DANSAKO, H, MATSUO, K, FUJII, K, SEZAKI, N, NAKAYAMA, H, YANO, T, FUKUDA, S
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aiolos gene
Alternative Splicing
Biological and medical sciences
Bone Marrow Cells - metabolism
Burkitt Lymphoma - genetics
Burkitt Lymphoma - metabolism
DNA-Binding Proteins
Female
Gene Expression
Genes, Dominant - genetics
Hematologic and hematopoietic diseases
Humans
Ikaros gene
Ikaros Transcription Factor
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Protein Isoforms - genetics
Protein Isoforms - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors - biosynthesis
Transcription Factors - genetics
Zinc Fingers - genetics
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Summary: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.
ISSN:0008-5472
1538-7445