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. LGL 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 the clinic and in basic research.