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Lymphoma

Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3

Leukemia volume 22, pages 393–399 (2008)Cite this article

Abstract

Sezary syndrome (SS) is a rare, aggressive CD4+ cutaneous T-cell lymphoma (CTCL); molecular traits differentiating SS from nonleukemic mycosis fungoides (MF) and from inflammatory skin diseases (ID) are not sufficiently characterized. Peripheral blood mononuclear cells (PBMC) of 10 SS patients and 10 healthy donors (HD) were screened by Affymetrix U133Plus2.0 chips for differential gene expression. Ten candidate genes were confirmed by qRT-PCR to be significantly overexpressed in CD4+ T cells of SS versus HD/ID. For easier clinical use, these genes were re-analyzed in PBMC; qRT-PCR confirmed five novel (DNM3, IGFL2, CDO1, NEDD4L, KLHDC5) and two known genes (PLS3, TNFSF11) to be significantly overexpressed in SS. Multiple logistic regression analysis revealed that CDO1 and DNM3 had the highest discriminative power in combination. Upon comparison of PBMC and skin samples of SS versus MF, CDO1 and DNM3 were found upregulated only in SS. Using anti-CDO1 antisera, differential expression of CDO1 protein was confirmed in SS CD4+ T cells. Interestingly, DNM3 and CDO1 are known to be regulated by SS-associated transcription factors TWIST1 and c-myb, respectively. Furthermore, CDO1 catalyzes taurine synthesis and taurine inhibits apoptosis and promotes chemoprotection. In summary, CDO1 and DNM3 may improve the diagnosis of SS and open novel clues to its pathogenesis.

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Acknowledgements

We thank Dr M Goebeler for critically reading the manuscript and Dr K Schledzewski, Mrs Arif-Said, Mrs Schmuttermaier and Mrs Demory for excellent technical assistance.

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Author notes

  1. N Booken and A Gratchev: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Ruprecht Karl University of Heidelberg, Mannheim, Germany

    N Booken, A Gratchev, J Utikal, M Qadoumi, E Dippel, C-D Klemke & S Goerdt

  2. Institute of Medical Statistics, University Medical Centre Mannheim, Ruprecht Karl University of Heidelberg, Mannheim, Germany

    C Weiß

  3. Medical Research Center (ZMF), University Medical Centre Mannheim, Ruprecht Karl University of Heidelberg, Mannheim, Germany

    X Yu

  4. Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria

    M Schmuth & N Sepp

  5. Department of Dermatology, University of Freiburg, Freiburg, Germany

    D Nashan

  6. Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Germany

    K Rass

  7. Department of Dermatology, University of Bonn, Bonn, Germany

    T Tüting

  8. Department of Dermatology, Charite-University Medicine Berlin, Berlin, Germany

    C Assaf

  9. Department of Dermatology, Academic Medical Centre, Lemgo, Germany

    E Dippel

  10. Department of Dermatology, Academic Medical Centre, Minden, Germany

    R Stadler

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  1. N Booken
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  2. A Gratchev
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  6. M Qadoumi
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  10. K Rass
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  11. T Tüting
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  12. C Assaf
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  13. E Dippel
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  14. R Stadler
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  15. C-D Klemke
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  16. S Goerdt
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Corresponding author

Correspondence to N Booken.

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

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Booken, N., Gratchev, A., Utikal, J. et al. Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3. Leukemia 22, 393–399 (2008). https://doi.org/10.1038/sj.leu.2405044

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