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.

  • Original Article
  • Published:

Chronic Lymphocytic Leukemia

Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies

Leukemia volume 25, pages 1439–1443 (2011)Cite this article

Subjects

Abstract

T-cell large granular lymphocytic (LGL) leukemia is a complex diagnosis, requiring persistent clonal expansions of LGLs, and cytopenias. Often the diagnosis is unclear as non-clonal expansions of LGLs commonly occur in reactive conditions. To better understand T-LGL leukemia, we performed a comprehensive clinicopathologic analysis of 85 patients with LGL expansions. Interestingly, distinct CD8+(dim)/CD57+ populations, seen by flow cytometry, were significantly associated with clonal T-LGL leukemia (P<0.001) as well as neutropenia (median absolute neutrophil count (ANC) 1.45 vs 3.19 × 109/l; P=0.0017). Furthermore, cases with distinct CD8+(dim)/CD57+ populations and monoclonal T cells had even lower ANCs (median ANC 1.41 × 109/l; P=0.001) compared with cases without these dual criteria. Additionally, complete or partial loss of CD5 expression was independently associated with clonal T-LGL leukemia (P<0.001) and neutropenia (median ANC 1.41 vs 2.70 × 109/l; P=0.002). This study describes specific immunophenotypic parameters to better define clonal cases of T-LGL leukemia associated with significant neutropenia.

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

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Rose MG, Berliner N . T-cell large granular lymphocyte leukemia and related disorders. Oncologist 2004; 9: 247–258.

    Article  Google Scholar 

  3. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. (ed). WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. IARC: Lyon, France, 2008.

    Google Scholar 

  4. Kreutzman A, Juvonen V, Kairisto V, Ekblom M, Stenke L, Seggewiss R et al. Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood 5; 116: 772–782.

    Article  Google Scholar 

  5. Morley JK, Batliwalla FM, Hingorani R, Gregersen PK . Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. J Immunol 1995; 154: 6182–6190.

    CAS  PubMed  Google Scholar 

  6. Bahceci E, Epperson D, Douek DC, Melenhorst JJ, Childs RC, Barrett AJ . Early reconstitution of the T-cell repertoire after non-myeloablative peripheral blood stem cell transplantation is from post-thymic T-cell expansion and is unaffected by graft-versus-host disease or mixed chimaerism. Br J Haematol 2003; 122: 934–943.

    Article  Google Scholar 

  7. Scotet E, Peyrat MA, Saulquin X, Retiere C, Couedel C, Davodeau F et al. Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T-cell clonal expansions found in autoimmune inflammatory processes. Eur J Immunol 1999; 29: 973–985.

    Article  CAS  Google Scholar 

  8. Morice WG, Kurtin PJ, Tefferi A, Hanson CA . Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B. Blood 2002; 99: 268–274.

    Article  CAS  Google Scholar 

  9. Lima M, Almeida J, Santos AH, dos Anjos Teixeira M, Alguero MC, Queiros ML et al. Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease. Am J Pathol 2001; 159: 1861–1868.

    Article  CAS  PubMed Central  Google Scholar 

  10. Lundell R, Hartung L, Hill S, Perkins SL, Bahler DW . T-cell large granular lymphocyte leukemias have multiple phenotypic abnormalities involving pan-T-cell antigens and receptors for MHC molecules. Am J Clin Pathol 2005; 124: 937–946.

    Article  CAS  Google Scholar 

  11. Lima M, Almeida J, Dos Anjos Teixeira M, Alguero Md Mdel C, Santos AH, Balanzategui A et al. TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. Am J Pathol 2003; 163: 763–771.

    Article  PubMed Central  Google Scholar 

  12. Droese J, Langerak AW, Groenen PJ, Bruggemann M, Neumann P, Wolvers-Tettero IL et al. Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies. Leukemia 2004; 18: 1531–1538.

    Article  CAS  Google Scholar 

  13. van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17: 2257–2317.

    Article  CAS  PubMed Central  Google Scholar 

  14. Gorochov G, Debre P, Leblond V, Sadat-Sowti B, Sigaux F, Autran B . Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation. Blood 1994; 83: 587–595.

    CAS  PubMed  Google Scholar 

  15. Mohty M, Faucher C, Vey N, Chabannon C, Sainty D, Arnoulet C et al. Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis. Leukemia 2002; 16: 2129–2133.

    Article  CAS  Google Scholar 

  16. Langerak AW, van Den Beemd R, Wolvers-Tettero IL, Boor PP, van Lochem EG, Hooijkaas H et al. Molecular and flow cytometric analysis of the Vbeta repertoire for clonality assessment in mature TCRalphabeta T-cell proliferations. Blood 2001; 98: 165–173.

    Article  CAS  Google Scholar 

  17. Morice WG, Kimlinger T, Katzmann JA, Lust JA, Heimgartner PJ, Halling KC et al. Flow cytometric assessment of TCR-Vbeta expression in the evaluation of peripheral blood involvement by T-cell lymphoproliferative disorders: a comparison with conventional T-cell immunophenotyping and molecular genetic techniques. Am J Clin Pathol 2004; 121: 373–383.

    Article  CAS  Google Scholar 

  18. Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA . Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia. Br J Haematol 2003; 120: 1026–1036.

    Article  CAS  Google Scholar 

  19. Brenchley JM, Karandikar NJ, Betts MR, Ambrozak DR, Hill BJ, Crotty LE et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 2003; 101: 2711–2720.

    Article  CAS  Google Scholar 

  20. Ohkawa T, Seki S, Dobashi H, Koike Y, Habu Y, Ami K et al. Systematic characterization of human CD8+ T cells with natural killer cell markers in comparison with natural killer cells and normal CD8+ T cells. Immunology 2001; 103: 281–290.

    Article  CAS  PubMed Central  Google Scholar 

  21. Sada-Ovalle I, Torre-Bouscoulet L, Valdez-Vazquez R, Martinez-Cairo S, Zenteno E, Lascurain R . Characterization of a cytotoxic CD57+ T-cell subset from patients with pulmonary tuberculosis. Clin Immunol 2006; 121: 314–323.

    Article  CAS  Google Scholar 

  22. Linn YC, Hui KM . Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma 2003; 44: 1457–1462.

    Article  CAS  Google Scholar 

  23. Wang EC, Taylor-Wiedeman J, Perera P, Fisher J, Borysiewicz LK . Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses. Clin Exp Immunol 1993; 94: 297–305.

    Article  CAS  PubMed Central  Google Scholar 

  24. Arber DA, Weiss LM . CD57: a review. Appl Immunohistochem 1995; 3: 137–152.

    CAS  Google Scholar 

  25. McNerlan SE, Rea IM, Alexander HD, Morris TC . Changes in natural killer cells, the CD57CD8 subset, and related cytokines in healthy aging. J Clin Immunol 1998; 18: 31–38.

    Article  CAS  Google Scholar 

  26. Huh YO, Medeiros LJ, Ravandi F, Konoplev S, Jorgensen JL, Miranda RN . T-cell large granular lymphocyte leukemia associated with myelodysplastic syndrome: a clinicopathologic study of nine cases. Am J Clin Pathol 2009; 131: 347–356.

    Article  CAS  Google Scholar 

  27. Saunthararajah Y, Molldrem JL, Rivera M, Williams A, Stetler-Stevenson M, Sorbara L et al. Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features. Br J Haematol 2001; 112: 195–200.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Susan Atwater, Yasodha Natkunam, Roger Warnke, Brent Tan, and Scott Boyd for their support.

Author information

Authors and Affiliations

  1. Department of Pathology, Stanford University Medical Center, Stanford, CA, USA

    R S Ohgami, I T Pereira, G Gitana, J L Zehnder & D A Arber

  2. Department of Sociology, Stanford University, Stanford, CA, USA

    J K Ohgami

  3. Department of Medicine, Stanford University Medical Center, Stanford, CA, USA

    J L Zehnder

Authors
  1. R S Ohgami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J K Ohgami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I T Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Gitana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J L Zehnder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D A Arber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R S Ohgami.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohgami, R., Ohgami, J., Pereira, I. et al. Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies. Leukemia 25, 1439–1443 (2011). https://doi.org/10.1038/leu.2011.107

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.107

Keywords

This article is cited by

Search

Advanced search

Quick links