Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Clonal T- and natural killer-cell large granular lymphocyte proliferations in a single patient established by array-based comparative genomic hybridization analysis

Leukemia volume 20, pages 2212–2214 (2006)Cite this article

Clonal large granular lymphocyte (LGL) proliferations can arise from their normal T- or natural killer (NK)-cell counterparts. Both T-LGL and chronic NK-LGL leukemia/lymphocytosis are well-recognized disease entities in the World Health Organization (WHO) classification of hematopoietic malignancies. LGL leukemia is a rare and heterogeneous disorder and most cases have an indolent clinical course. Its main clinical manifestations are related to chronic neutropenia and/or anemia.1

Clonality assessment studies are essential to discriminate true LGL leukemia from other reactive proliferations. In T-LGL proliferations, clonality can easily be detected by PCR analysis of T-cell receptor (TCR) genes. In NK-LGL proliferations, clonality detection is difficult owing to the absence of specific clonality markers. Currently it is therefore unclear whether indolent NK-LGL leukemia, also known as chronic NK-LGL lymphocytosis or indolent NK-cell lymphoproliferative disorder, represents a reactive polyclonal process or a chronic phase of leukemia.1 It was recently demonstrated that the NK cells in patients with molecularly (HUMARA X inactivation assay in female patients) proven monoclonal chronic NK-LGL lymphocytosis express an aberrant CD56−/+dim/CD11b−/+dim immunophenotype.2 This immunophenotype is clearly different from the phenotype found in aggressive NK-cell leukemia and normal or reactive/activated NK-cell proliferations, which generally show high CD56 expression and a higher reactivity for CD11b. The aberrant immunophenotype of these NK-LGL cells could reflect underlying clonal genetic abnormalities.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Sokol L, Loughran Jr TP . Large granular lymphocyte leukemia. Oncologist 2006; 11: 263–273.

    Article  CAS  Google Scholar 

  2. Lima M, Almeida J, Montero AG, Teixeira Mdos A, Queiros ML, Santos AH et al. Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56−/+dim chronic natural killer cell large granular lymphocytosis. Am J Pathol 2004; 165: 1117–1127.

    Article  CAS  Google Scholar 

  3. Wlodarski MW, O'Keefe C, Howe EC, Risitano AM, Rodriguez A, Warshawsky I et al. Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell-receptor restriction in large granular lymphocyte leukemia. Blood 2005; 106: 2769–2780.

    Article  CAS  Google Scholar 

  4. Sandberg Y, Almeida J, Gonzalez M, Lima M, Barcena P, Szczepanski T et al. TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells. Leukemia 2006; 20: 505–513.

    Article  CAS  Google Scholar 

  5. Zambello R, Loughran Jr TP, Trentin L, Pontisso P, Battistella L, Raimondi R et al. Serologic and molecular evidence for a possible pathogenetic role of viral infection in CD3-negative natural killer-type lymphoproliferative disease of granular lymphocytes. Leukemia 1995; 9: 1207–1211.

    CAS  PubMed  Google Scholar 

  6. Raap AK, van der Burg MJ, Knijnenburg J, Meershoek E, Rosenberg C, Gray JW et al. Array comparative genomic hybridization with cyanin cis-platinum-labeled DNAs. Biotechniques 2004; 37: 130–134.

    Article  CAS  Google Scholar 

  7. Pulford K, Banham AH, Lyne L, Jones M, Ippolito GC, Liu H et al. The BCL11AXL transcription factor: its distribution in normal and malignant tissues and use as a marker for plasmacytoid dendritic cells. Leukemia 2006; 20: 1439–1441.

    Article  CAS  Google Scholar 

  8. Kondo H, Watanabe J, Iwasaki H . T-large granular lymphocyte leukemia accompanied by an increase of natural killer cells (CD3−) and associated with ulcerative colitis and autoimmune hepatitis. Leuk Lymphoma 2001; 41: 207–212.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank K van Lom (Department of Hematology, Erasmus MC) and H Rijksen (Department of Clinical Chemistry, Diakonessenhuis) for cytomorphological analysis; KH Lam (Department of Pathology, Erasmus MC) and HW Ruitenberg (Department of Pathology, Diakonessenhuis) for histopathological analysis; EFE de Haas for purification of cell populations and WM Comans-Bitter for preparing the figures.

Author information

Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Y Sandberg, D Tielemans, I L M Wolvers-Tettero, J J M van Dongen & A W Langerak

  2. Department of Internal Medicine, Diakonessenhuis, Utrecht, The Netherlands

    V O Dezentjé & R van der Griend

  3. Department of Molecular cell biology, Leiden University Medical Center, Leiden, The Netherlands

    K Szuhai

  4. Department of Clinical Chemistry, Medical Microbiology, and Immunology, Diakonessenhuis, Utrecht, The Netherlands

    A J van Houte

Authors
  1. Y Sandberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V O Dezentjé
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Szuhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A J van Houte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Tielemans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I L M Wolvers-Tettero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J J M van Dongen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R van der Griend
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A W Langerak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A W Langerak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sandberg, Y., Dezentjé, V., Szuhai, K. et al. Clonal T- and natural killer-cell large granular lymphocyte proliferations in a single patient established by array-based comparative genomic hybridization analysis. Leukemia 20, 2212–2214 (2006). https://doi.org/10.1038/sj.leu.2404451

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404451

Search

Advanced search

Quick links