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Treatment of large granular lymphocyte leukemia

Thierry Lamy, MD, PhD
Thomas P Loughran, Jr, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


Large granular lymphocyte (LGL) leukemia is characterized by peripheral blood and marrow lymphocytic infiltration with clonal LGLs, splenomegaly, and cytopenias, most commonly neutropenia.

The LGL is a morphologically distinct lymphoid subset that is larger than most circulating lymphocytes, and has characteristic azurophilic granules containing acid hydrolases (picture 1). LGLs comprise 10 to 15 percent of normal peripheral blood mononuclear cells. The absolute number of LGLs in the peripheral blood of normal subjects is 200 to 400/microL.

LGLs arise from two major lineages [1,2]. About 85 percent of normal LGLs have an NK cell phenotype, and only 15 percent are derived from T cells. The phenotypes of LGLs in LGL leukemia, however, are just the opposite:

CD3 positive T cell lineage — Approximately 85 percent of circulating LGLs are CD3 positive, CD57 positive, CD56 negative T cells, representing in vivo antigen-activated effector-memory cytotoxic T cells.

CD3 negative NK cell lineage — The remaining 15 percent of circulating LGLs are 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.


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Literature review current through: Jul 2017. | This topic last updated: Sep 09, 2015.
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