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  • Oncogenomics
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A genomic analysis of adult T-cell leukemia

Oncogene volume 26, pages 1245–1255 (2007)Cite this article

Abstract

Adult T-cell leukemia (ATL) is an intractable malignancy of CD4+ T cells that is etiologically associated with infection by human T-cell leukemia virus-type I. Most individuals in the chronic stage of ATL eventually undergo progression to a highly aggressive acute stage. To clarify the mechanism responsible for this stage progression, we isolated CD4+ cells from individuals in the chronic (n=19) or acute (n=22) stages of ATL and subjected them to profiling of gene expression with DNA microarrays containing >44 000 probe sets. Changes in chromosome copy number were also examined for 24 cell specimens with the use of microarrays harboring ∼50 000 probe sets. Stage-dependent changes in gene expression profile and chromosome copy number were apparent. Furthermore, expression of the gene for MET, a receptor tyrosine kinase for hepatocyte growth factor (HGF), was shown to be specific to the acute stage of ATL, and the plasma concentration of HGF was increased in individuals in either the acute or chronic stage. HGF induced proliferation of a MET-positive ATL cell line, and this effect was blocked by antibodies to HGF. The HGF-MET signaling pathway is thus a potential therapeutic target for ATL.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

ATL:

Adult T-cell leukemia

PCR:

polymerase chain reaction

PHA:

phytohemagglutinin

ANN:

artificial neural network

CNA:

copy number alterations

HGF:

hepatocyte growth factor

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Acknowledgements

This study was supported in-part by a grant for Third-Term Comprehensive Control Research for Cancer from the Ministry of Health, Labor and Welfare of Japan, and by a grant for Scientific Research on Priority Areas ‘Applied Genomics’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Division of Functional Genomics, Jichi Medical University, Shimotsukeshi, Tochigi, Japan

    Y L Choi, Y Yamashita, R Kaneda, S Takada & H Mano

  2. Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan

    K Tsukasaki, Y Onimaru & M Tomonaga

  3. Department of Biological Sciences, University of Maryland, Baltimore, MD, USA

    M C O'Neill

  4. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan

    Y Yamada & S Kamihira

  5. Division of Molecular Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    K Matsumoto & T Nakamura

  6. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    J Ohashi

  7. Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan

    S Tsutsumi & H Aburatani

  8. CREST, Japan Science and Technology Agency, Saitama, Japan

    H Mano

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  1. Y L Choi
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  2. K Tsukasaki
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Corresponding author

Correspondence to H Mano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Choi, Y., Tsukasaki, K., O'Neill, M. et al. A genomic analysis of adult T-cell leukemia. Oncogene 26, 1245–1255 (2007). https://doi.org/10.1038/sj.onc.1209898

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