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Chronic Lymphocytic Leukemia

The candidate immunotherapeutical target, the receptor for hyaluronic acid-mediated motility, is associated with proliferation and shows prognostic value in B-cell chronic lymphocytic leukemia

Leukemia volume 23, pages 519–527 (2009)Cite this article

Abstract

Differential expression of molecules in chronic lymphocytic leukemia (CLL) may define prognostic markers and suitable targets for immunotherapy. Expression of the tumor-associated antigen (TAA) RHAMM (receptor for hyaluronic acid-mediated motility) as well as RHAMM splicing variants was assessed in series of 72 CLL patients. Quantitative reverse transcriptase PCR showed higher RHAMM expression in high-risk CLL patients, as well as in the advanced stages of the disease. CLL cases with a higher RHAMM expression showed a significantly shorter median treatment-free survival. Among patients with mutated immunoglobulin heavy chain genes, an analysis of RHAMM expression enabled to distinguish subgroup of patients with favorable prognosis. In lymph nodes, RHAMM staining correlated with a higher Ki-67 index and CD40L expression. Functionally, stimulation with CD40L enhanced RHAMM expression in CLL. We further characterized RHAMM-specific CD8+ T cells in patients with CLL, as the expression of TAAs might influence the clinical outcome by the means of immune reactions. The cytotoxic potential of RHAMM-specific T cells was shown against target cells bearing RHAMM-derived epitope as well as against CLL cells expressing RHAMM. In conclusion, RHAMM expression appears to be of prognostic value, as well as may reflect the proliferative capacity of CLL cells, and might therefore represent interesting target for immunotherapy.

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Acknowledgements

We would like to thank Ms Sabrina Kless, Alexandra Brodbeck and Ms Paulina Wlasiuk for the excellent technical support. We also appreciate the support from Perlan Technologies Polska in our analysis of the splicing variants of RHAMM.

Funding: This study was supported by grants from the Polish Scientific Committee KBN N402 034 31/1138 and N402 107 32/3496 as well as Deutsche Krebshilfe (106142 and 108060), Deutsche José Carreras Leukämie-Stiftung e.V.R 05/25 and Else Kröner-Fresenius-Stiftung A85/06. K.G. was supported by a generous scholarship from the Foundation for Polish Science.

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Authors and Affiliations

  1. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    K Giannopoulos, D Mertens, A Bühler, I Idler, A Kröber, J Greiner, H Döhner, S Stilgenbauer & M Schmitt

  2. Department of Hematooncology, Medical University of Lublin, Lublin, Poland

    K Giannopoulos, S Chocholska & A Dmoszyñska

  3. Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland

    K Giannopoulos & J Roliñski

  4. Junior Group ‘Mechanisms of Leukemogenesis’, DKFZ, Heidelberg, Germany

    D Mertens & I Idler

  5. Institute for Pathology, University of Ulm, Ulm, Germany

    T F E Barth & P Möller

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  1. K Giannopoulos
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Correspondence to K Giannopoulos.

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

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Giannopoulos, K., Mertens, D., Bühler, A. et al. The candidate immunotherapeutical target, the receptor for hyaluronic acid-mediated motility, is associated with proliferation and shows prognostic value in B-cell chronic lymphocytic leukemia. Leukemia 23, 519–527 (2009). https://doi.org/10.1038/leu.2008.338

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