Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia

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. NihoK. Takenaka, K. Shinagawa, K. Ikeda, K. Niiya, M. Harada

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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.

Original languageEnglish
Pages (from-to)4062-4065
Number of pages4
JournalCancer Research
Volume60
Issue number15
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., ... Harada, M. (2000). Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia. Cancer Research, 60(15), 4062-4065.