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Non-DNA-binding Ikaros isoform gene expressed in adult B-precursor acute lymphoblastic leukemia

Leukemia volume 16, pages 1285–1292 (2002)Cite this article

Abstract

Ikaros, a zinc finger transcription factor, is essential for lymphoid development. Mutant mice expressing dominant-negative Ikaros gene (Ikaros) isoforms develop an aggressive form of lymphoid malignancies. We examined the expression of Ikaros isoforms in 11 leukemic cell lines and adult acute lymphoblastic leukemia cells from 36 patients with B-precursor acute lymphoblastic leukemia (pre-B ALL) and nine with T-precursor acute lymphoblastic leukemia (pre-T ALL), using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In one pre-B ALL cell line, INC cells, and primary leukemic cells from 16 patients with pre-B ALL, we found the predominant expression of a non-DNA-binding Ikaros isoform, Ik-6. However, Ik-6 was not detected in pre-T ALL cells. All of pre-B ALL cells expressing Ik-6 were CD10+, whereas CD10− pre-B ALL cells did not express Ik-6. The expression of Ik-6 was not related to karyotype abnormalities such as t(9;22) and t(4;11). Proteins from the cells that expressed Ik-6 alone failed to bind to the Ikaros protein-specific binding sequence in DNA. Ikaros proteins lacking the DNA binding sequences were detected in the cytoplasm but not in the nucleus of the cells. When INC and primary pre-B ALL cells that express Ik-6 alone were irradiated and cultured in the absence of serum, these cells produced functional Ikaros isoforms, Ik-1 and Ik-2. Purified CD19+ CD10− and CD19+ CD10+ cells from normal human bone marrow did not express Ik-6. The predominant expression of Ik-6, which is the result of post-transcription dysregulation, is characteristic of adult pre-B ALL, especially CD10+ pre-B ALL.

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Acknowledgements

We thank Professor MF Greaves and Dr T Ford (Leukemia Research Fund Centre at the Institute of Cancer Research, London, UK) for helpful discussion. We also thank Professor K Georgopoulos (Massachusetts General Hospital, Harvard Medical School, Boston, MA) for providing the anti-Ikaros antibody and we thank Ms C Atsumaru (Fujisawa Pharmaceutical Co Ltd, Osaka, Japan) for providing technical advice. This work was supported by research grants from the Ministry of Education, Culture, Sports, Science, and Technology and from the Ministry of Health, Labour, and Welfare, Japan and a Grant-in-Aid from the Mie Medical Research Foundation.

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Authors and Affiliations

  1. The Second Department of Internal Medicine, Mie University School of Medicine, Mie, Japan

    K Nishii, N Katayama, E Usui, M Masuya, H Araki, F Lorenzo & H Shiku

  2. The Second Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan

    H Miwa & M Shikami

  3. Department of Molecular Pathology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co Ltd, Osaka, Japan

    T Ogawa

  4. Department of Internal Medicine, Hiroshima Red Cross Hospital, Hiroshima, Japan

    T Kyo

  5. Department of Internal Medicine, Osaka Red Cross Hospital, Osaka, Japan

    K Nasu

  6. Tokura Hospital, Kyoto, Japan

    K Kita

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Nishii, K., Katayama, N., Miwa, H. et al. Non-DNA-binding Ikaros isoform gene expressed in adult B-precursor acute lymphoblastic leukemia. Leukemia 16, 1285–1292 (2002). https://doi.org/10.1038/sj.leu.2402533

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