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]:
- 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.
LGL leukemia can arise from the clonal proliferation of LGLs of T cell or NK cell lineage. The management of LGL leukemia will be discussed here. The etiology, clinical features, and diagnosis of T cell LGL leukemia and the diagnosis and management of NK cell LGL leukemia are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia" and "Large granular lymphocyte leukemia in rheumatoid arthritis" and "Natural killer (NK) cell large granular lymphocyte leukemia".)