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T Cell Leukemias

TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells

Leukemia volume 20, pages 505–513 (2006)Cite this article

Abstract

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRαβ. Much less is known about the characteristics and pathogenesis of TCRγδ+ cases. We evaluated 44 patients with clonal TCRγδ+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRγδ+ T-LGL leukemia patients had similar clinical presentations as TCRαβ+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias – neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) – and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vγ9/Vδ2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vδ1, reflecting the TCR-spectrum of normal TCRγδ+ T-cells in adult PB. Identification of the well-defined post-thymic Vδ2-Jδ1 selection determinant in all evaluable Vγ9+/Vδ2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRγδ+ T-LGL leukemia patients.

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Acknowledgements

We are grateful to the following clinicians and/or scientists for sending in valuable samples: HJ Adriaansen, PB Berendes, H Berenschot, A Brand, M Diamant, A Ermens, JW Gratama, JC Grutters, EJ Harthoorn-Lasthuizen, C van der Heul, GW van Imhoff, U Jäger, W Kuis, HM Lokhorst, WAF Marijt, JW Smit, FAA Valster, E van Voorst tot Voorst, G Vreugdenhil, MJ Wondergem. We thank K van Lom and PB Berendes for cytomorphological analysis and WM Comans-Bitter for preparing the figures and for performing the detailed studies on TCRγδ expression and Vγ9, Vδ1, and Vδ2 usage in healthy controls. This study has been supported by a grant from the Dutch Cancer Society (to YS) and partially supported by the following grants: Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo, Madrid, Spain (grant FIS 02/1244), the Consejería de Educación y Cultura, Junta de Castilla y Léon, Valladolid, Spain (grant SA 103/03) and the University of Salamanca, Salamanca, Spain (Ref. No. 430 to PB).

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

    Y Sandberg, T Szczepañski, E J van Gastel-Mol, H Wind, J J M van Dongen & A W Langerak

  2. Service of Cytometry and Department of Medicine, University of Salamanca, Salamanca, Spain

    J Almeida, P Bárcena & A Orfao

  3. Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigación del Cancer (CSIC-USAL), Salamanca, Spain

    J Almeida, M Gonzalez, P Bárcena, A Balanzategui, J F San Miguel & A Orfao

  4. Service of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain

    M Gonzalez, A Balanzategui & J F San Miguel

  5. Service of Hematology, Hospital Geral de Santo António, Porto, Portugal

    M Lima

  6. Department of Pediatric Hematology and Oncology, Silesian Medical Academy, Zabrze, Poland

    T Szczepañski

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  1. Y Sandberg
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Correspondence to A W Langerak.

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Sandberg, Y., Almeida, J., Gonzalez, M. et al. TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells. Leukemia 20, 505–513 (2006). https://doi.org/10.1038/sj.leu.2404112

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