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Chronic lymphoproliferative disorder of natural killer cells: a distinct entity with subtypes correlating with normal natural killer cell subsets

Leukemia volume 24, pages 881–884 (2010)Cite this article

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The phenomenon of persistent natural killer (NK) cell lymphocytosis has recently been recognized as the provisional diagnostic entity ‘chronic lymphoproliferative disorder of natural killer cells’ (CLDNK) in the WHO (World Health Organization) classification of hematopoietic tumors.1 CLDNK, which has also been known as the NK-type lymphoproliferative disorder of granular lymphocytes, is generally considered indolent, although there are few published cases.2, 3, 4 The paucity of literature suggests that CLDNK is rare; however, disease recognition is problematic because NK cells lack a uniquely rearranged antigen receptor gene (such as T-cell receptor) to serve as a marker of clonal cellular expansion and to facilitate distinction from reactive processes. This feature renders flow cytometric immunophenotyping (FCIP) particularly important in diagnosing CLDNK, typically revealing CD16-positive and CD3-negative NK cells with diminished expression of CD56 and altered expression of a group of NK cell-associated receptors, which recognize major histocompatibility complex I and related antigens collectively referred to as NKRs. Abnormalities in NKRs recognized in CLDNKs include aberrancies in killer cell immunoglobulin-like receptor (KIR) and/or CD94 expression.3, 5 Although these patterns of NKR expression have been shown to distinguish CLDNKs from normal controls, transient NK cell lymphocytosis with abnormal NKR expression has also been reported; therefore, repeat studies are generally recommended for the confirmation of a CLDNK diagnosis, although the utility of this practice has yet to be formally established.3, 6, 7

Functionally and immunophenotypically distinct mature NK cell subsets, often referred to as CD56bright and CD56dim NK cells, based on their differential expression of this antigen, have recently been identified. CD56bright NK cells are found primarily in secondary lymphoid tissues, are brightly NKp46 positive, dimly CD16 positive, have little or no KIR expression and have limited cytotoxic potential, functioning primarily through the elaboration of cytokines, such as interferon-γ. In contrast, CD56dim NK cells are found primarily in the peripheral blood, are dimly NKp46 positive, brightly CD16 positive, frequent KIR expressers and act primarily as cytotoxic effector cells. Although these NK cell subsets have disparate attributes, they are closely inter-related to CD56dim NK cells derived from CD56bright NK cells through activation and exposure to cytokines, such as interleukin-12 and interleukin-15.8

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References

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, 2008, pp 439.

    Google Scholar 

  2. Epling-Burnette PK, Painter JS, Chaurasia P, Bai F, Wei S, Djeu JY et al. Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes. Blood 2004; 103: 3431–3439.

    Article  CAS  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Zambello R, Trentin L, Ciccone E, Bulian P, Agostini C, Moretta A et al. Phenotypic diversity of natural killer (NK) populations in patients with NK-type lymphoproliferative disease of granular lymphocytes. Blood 1993; 81: 2381–2385.

    CAS  PubMed  Google Scholar 

  5. Zambello R, Falco M, Della C M, Trentin L, Carollo D, Castriconi R et al. Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes. Blood 2003; 102: 1797–1805.

    Article  CAS  PubMed  Google Scholar 

  6. Pascal V, Schleinitz N, Brunet C, Ravet S, Bonnet E, Lafarge X et al. Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditions. Eur J Immunol 2004; 34: 2930–2940.

    Article  CAS  PubMed  Google Scholar 

  7. Zambello R, Loughran Jr TP, Trentin L, Rassu M, Facco M, Bortolin M et al. Spontaneous resolution of p58/EB6 antigen restricted NK-type lymphoproliferative disease of granular lymphocytes: role of Epstein–Barr virus infection. Br J Haematol 1997; 99: 215–221.

    Article  CAS  PubMed  Google Scholar 

  8. Romagnani C, Juelke K, Falco M, Morandi B, D’Agostino A, Costa R et al. CD56brightCD16-killer Ig-like receptor-NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol 2007; 178: 4947–4955.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Divisions of Hematopathology, Mayo Clinic, Rochester, MN, USA

    W G Morice, D Jevremovic, A Roden, C A Hanson & P J Kurtin

  2. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA

    H Olteanu & S Kroft

  3. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    G Nowakowski

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  1. W G Morice
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  2. D Jevremovic
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  7. C A Hanson
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  8. P J Kurtin
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Correspondence to W G Morice.

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Morice, W., Jevremovic, D., Olteanu, H. et al. Chronic lymphoproliferative disorder of natural killer cells: a distinct entity with subtypes correlating with normal natural killer cell subsets. Leukemia 24, 881–884 (2010). https://doi.org/10.1038/leu.2009.304

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