T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias

Abstract

Large granular lymphocyte (LGL) leukemia is a rare disorder of cytotoxic lymphocytes. LGL cells play an integral role in the immune system and are divided into two major lineages of CD3− natural killer (NK) cells and CD3+ T cells that circulate throughout the blood in search of infected cells, in which they will make contact through a receptor ligand and induce cell death. LGLs cells are also programmed to undergo apoptosis after contact with an infected target cell; however they continue to survive in individuals with LGL leukemia. This unchecked proliferation and cytotoxicity of LGLs in patients results in autoimmunity or malignancy. Rheumatoid arthritis is the most common autoimmune condition seen in individuals with LGL leukemia; however, LGL leukemia is associated with a wide spectrum of other autoimmune diseases. Patients may also suffer from other hematological conditions including hemolytic anemia, pure red cell aplasia, and neutropenia which lead to recurrent bacterial infections. Currently, the only established treatment involves a low dose of an immunosuppressive regimen with methotrexate, in which 40–50% of patients are either resistant or do not respond. In order to establish new therapeutics it is important to understand the current state of LGL leukemia both in clinic and in basic research.

The pathogenesis and treatment of large granular lymphocyte leukemia

“…Large granular lymphocyte leukemia embodies a spectrum of rare clonal lymphoproliferative disorders, all which involve inappropriate expansion of large granular lymphocytes (LGLs); either cytotoxic T-lymphocytes (CTLs) or natural killer (NK) cells 1, 2 . In normal adults, LGLs represent 10–15% of peripheral blood mononuclear cells (PBMCs) and can be classified into two distinct lineages as either CD3+ CTLs or CD3- NK cells.…”

MicroRNA regulation of natural killer cells

“…Most of the existing literature regarding the role of NK miRNAs in disease focuses on NK cell malignancies. Rare cancers arising from NK cells can take multiple forms with various degrees of aggression, from chronic NK cell lymphocytosis, to aggressive nasal-type NK/T cell lymphoma, to highly aggressive NK cell leukemia/lymphoma (Ishida and Kwong, 2010; Watters et al, 2011; Semenzato et al, 2012). …”

Atypical aleukemic presentation of large granular lymphocytic leukemia: a case report

“…T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disease characterized by the accumulation of a monoclonal T- or natural killer (NK)-lymphocyte population in the bone marrow, blood, spleen, and liver 1,2…”