Natural killer (NK) cell large granular lymphocyte leukemia
- Thierry Lamy, MD, PhD
Thierry Lamy, MD, PhD
- Professor in Hematology
- University of Rennes, France
- Thomas P Loughran, Jr, MD
Thomas P Loughran, Jr, MD
- Director, University of Virginia Cancer Center
- University of Virginia
Large granular lymphocyte (LGL) leukemia is characterized by peripheral blood and marrow lymphocytic infiltration with clonal LGLs, splenomegaly, and cytopenias, most commonly neutropenia. LGL leukemia arises most frequently from a T cell lineage (85 percent) or, less commonly, from a natural killer (NK) cell lineage (15 percent) [1,2]. The etiology, clinical features, diagnosis, and treatment of NK cell LGL disorders will be discussed here. T cell LGL leukemia is discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia" and "Treatment of large granular lymphocyte leukemia".)
THE LARGE GRANULAR LYMPHOCYTE
The large granular lymphocyte (LGL) is a morphologically distinct lymphoid subset comprising 10 to 15 percent of normal peripheral blood mononuclear cells (picture 1). The absolute number of LGLs in the peripheral blood of normal subjects is 200 to 400/microL. LGLs arise from two major lineages:
●CD3 positive, CD 57 positive, CD56 negative T cells, representing in vivo antigen-activated cytotoxic effector T cells
●CD3-, CD56+ natural killer (NK) cells. It had been postulated that such NK cells mediate non-major histocompatibility complex (MHC)-restricted cytotoxicity. It is now established that NK cells possess specific receptors for MHC class I molecules named "killer-cell Ig-like inhibitory receptor" (KIR) and "killer-cell activating receptor" (KAR). Interactions between these receptors and MHC class I molecules on target cells may inhibit or activate NK cell-mediated cytotoxicity.
Secondary benign (nonclonal) LGL expansions have been reported in the following clinical situations:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- THE LARGE GRANULAR LYMPHOCYTE
- Classification of LGL disorders
- CHRONIC NK CELL LYMPHOCYTOSIS
- Etiology and pathogenesis
- Clinical features and prognosis
- Laboratory findings
- AGGRESSIVE NK CELL LEUKEMIA
- Clinical presentation
- Laboratory findings
- Differential diagnosis
- - Extranodal NK/T cell lymphoma, nasal type
- - Blastic plasmacytoid dendritic cell neoplasm
- - Blastic NK cell lymphoma
- CLINICAL TRIALS
- SUMMARY AND RECOMMENDATIONS