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Lymphoma

Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma

Leukemia volume 23, pages 2129–2138 (2009)Cite this article

Abstract

Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK− and cutaneous ALK− ALCL (cALCL). Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK− ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of five ALK+ and four ALK− systemic ALCL, seven cALCL and sixteen cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4+, CD8+ or CD30+ T-cell origin. Indeed, ALCL display a down-modulation of many T-cell characteristic molecules. All ALCL types show significant expression of NFκB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly, few genes are differentially expressed between systemic and cALCL despite their different clinical behaviour, and between ALK− ALCL and cHL despite their different cellular origin. ALK+ ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.

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Acknowledgements

We highly appreciate the excellent technical assistance of Ralf Lieberz, Nicole Dieckert, Yvonne Michel, Ingrid Kremser and Klaus Lennartz. We thank Dr Detlef Güssow and Melanie Kühnl from Merck KGaA, Darmstadt, Germany for the opportunity to scan the Affymetrix arrays in their laboratory. This work was supported by grants from the Deutsche Forschungsgemeinschaft (KU1315/5-2, BR1238/6-2 and 6-3 and WI2015/1-1), the Deutsche Krebshilfe and the Associazione Italiana per la Ricerca sul Cancro (AIRC). Enrico Tiacci was recipient of a fellowship (F 05/01) granted by the German José Carreras Leukemia Foundation.

Author information

Author notes

  1. R Küppers and M-L Hansmann: These two authors contributed equally to this work.

Authors and Affiliations

  1. Senckenberg Institute for Pathology, University of Frankfurt, Medical School, Frankfurt/Main, Germany

    S Eckerle, V Brune, C Döring, K Willenbrock, A Bräuninger & M-L Hansmann

  2. Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany

    S Eckerle, V Brune, E Tiacci, V Bohle & R Küppers

  3. Institute for Informatics, University of Frankfurt, Frankfurt, Germany

    C Döring & D Metzler

  4. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden

    C Sundström

  5. Department of Pathology and Molecular Medicine, 2nd Medical School, Charles University, Prague, Czech Republic

    R Kodet

  6. Institute for Anatomical Pathology, Policlinico S. Matteo, University of Pavia, Pavia, Italy

    M Paulli

  7. Institute of Hematology, University of Perugia, Perugia, Italy

    B Falini

  8. Institute for Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    W Klapper

  9. Institute for Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    A B Chaubert

  10. Institute for Pathology, University of Münster, Münster, Germany

    A Bräuninger

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Correspondence to R Küppers.

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

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Eckerle, S., Brune, V., Döring, C. et al. Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma. Leukemia 23, 2129–2138 (2009). https://doi.org/10.1038/leu.2009.161

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