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In situ leukemic plasmacytoid dendritic cells pattern of chemokine receptors expression and in vitro migratory response

Leukemia volume 18, pages 1491–1498 (2004)Cite this article

Abstract

Plasmacytoid dendritic cell (PDC) leukemia/lymphoma is a rare neoplasm presenting cutaneous lesions at the time of diagnosis, followed by dissemination to bone marrow, lymph nodes, and other lymphoid and nonlymphoid organs. Since these leukemic counterparts of human PDC are similar to normal PDC, we studied their chemokine receptor equipment and their migratory capacities. We found both in skin lesions and in invaded lymph nodes an expression by tumor cells of CXCR3, CXCR4, and CCR7, and the concomitant expression by cells in the microenvironment of their respective ligands CXCL9, CXCL12, and CCL19. Moreover, flow cytometry phenotype of leukemic PDC (LPDC) revealed an unexpected expression of CCR6. We show that fresh tumor cells are able to migrate in response to CXCR4, CCR2, CCR5, CCR6, and CCR7 ligands, and the ability of CXCR3 ligands to increase the responsiveness to CXCL12. IL-3- or virus-induced activation of LPDC leads to downregulation of CXCR3 and CXCR4, and upregulation of CCR7, associated with the loss of response to CXCL12, and the acquisition of sensitivity to CCL19. Altogether, these results suggest that the preferential accumulation of LPDC in the skin or lymph nodes could be orchestrated by CXCR3, CXCR4, CCR6, and CCR7 ligands, found in nontumoral structures of invaded organs.

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Acknowledgements

We are grateful to Laurence Grossi for her technical assistance. We thank Drs Véronique Deneys (UCL Saint Luc, Bruxelles), Rémy Gressin (CHU Grenoble), Emilienne Kuhlein (CHU Toulouse), Marc Maynadié (CHU Dijon), Hubert Orfeuvre (CHR Bourg en Bresse), Véronique Salaün (CHU Caen), and the GEIL (Groupe d'Etude Immunologique des Leucémies) for providing us with tumor cells. We are grateful to Jean-Paul Molens, Olivier Manches, Gabrielle Lui, Juliette Angel, and Ariane Blum for their efficiency in the laboratory. We thank Dr MF Sotto (CHU Grenoble) for help with microscopy. This work was supported by grant nos. 4498 and 4798 from ARC (Association pour la Recherche sur le Cancer), and grant no. 2003.26 from EFS (Etablissement Français du Sang).

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Author notes

  1. N Bendriss-Vermare

    Present address: INSERM U590, Centre Léon Bérard, Lyon, France

  2. N Bendriss-Vermare and L Chaperot: These two authors contributed equally to this work

Authors and Affiliations

  1. Schering Plough Laboratory for Immunological Research, Dardilly, France

    N Bendriss-Vermare, B Vanbervliet, F Briere & C Caux

  2. Department of Research and Development, EFS Rhône-Alpes Grenoble, La Tronche, France

    L Chaperot, M-C Jacob, J-C Bensa & J Plumas

  3. Department pathology, CHU Bellevue, Saint Etienne, France

    M Peoc'h

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Correspondence to L Chaperot.

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Bendriss-Vermare, N., Chaperot, L., Peoc'h, M. et al. In situ leukemic plasmacytoid dendritic cells pattern of chemokine receptors expression and in vitro migratory response. Leukemia 18, 1491–1498 (2004). https://doi.org/10.1038/sj.leu.2403452

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