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Molecular Cytogenetics and Cytogenetics

Heterogeneous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation

Leukemia volume 14, pages 1621–1629 (2000)Cite this article

Abstract

We report the characterization of a rare chromosomal translocation, a t(2;11)(q31;p15), which occurred in a patient with de novo acute myeloid leukemia (AML-M4). By 3′-RACE and RT-PCR analyses, two kinds of NUP98-HOXD13 fusion transcript were detected. In addition, we identified a novel fusion transcript, NUP98-FN1, in the same patient. Ectopic expression of the wild-type HOXD13 gene was also observed in the patient, suggesting that HOXD13 contributes to the development of this type of leukemia. The NUP98-HOXD13 fusion transcript was predicted to encode a 552 or 569-amino acid protein containing the Phe-Gly (FG) repeat region of NUP98 and the homeodomain of HOXD13. The NUP98-FN1 fusion transcript was predicted to encode a 482 or 499-amino acid protein consisting of the same N-terminal region of NUP98 and a C-terminal region of 12 amino acids derived from a previously unidentified sequence. We isolated and characterized the chromosomal breakpoints. The breakpoint at 11p15 is mapped within a LINE repetitive element in a 9 kb intron of NUP98, and more than 60% of the sequenced 3 kb region surrounding the breakpoint junction consists of repetitive elements. The other breakpoint at 2q31 is in an intron of FN1, which is located 7 kb upstream of HOXD13, and the repetitive sequence content of the breakpoint junction is low. Local sequence duplications at genomic breakpoints suggest that the t(2;11) translocation is mediated through staggered double-strand DNA breaks. These results throw light on the mechanisms responsible for the generation of t(2;11) translocation and on the processes leading to t(2;11) leukemia. Leukemia (2000) 14, 1621–1629.

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Acknowledgements

We are grateful to Drs H Ichikawa and F Morohoshi for critical reading of the manuscript. We also thank M Fukushima, M Mori and C Hatanaka for their technical assistance. This work was supported in part by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan and by a Grant-in-Aid for Research on Human Genome and Gene Therapy from the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. Cancer Genomics Division, National Cancer Center Research Institute, Tokyo, Japan

    Y Arai, K Arai & M Ohki

  2. Fourth Department of Internal Medicine, Hiroshima Red Cross Hospital, Hiroshima, Japan

    T Kyo

  3. Second Department of Internal Medicine, Aichi Medical University, Aichi, Japan

    H Miwa

  4. Department of Cancer Cytogenetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    N Kamada

  5. Second Department of Internal Medicine, Mie University, Mie, Japan

    K Kita

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Arai, Y., Kyo, T., Miwa, H. et al. Heterogeneous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation. Leukemia 14, 1621–1629 (2000). https://doi.org/10.1038/sj.leu.2401881

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