Large granular lymphocytic leukemia and its association with immune dysregulation

Abstract

Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disease of cytotoxic T cells or NK cells with LGL morphology and frequently complicated cytopenia and/or different autoimmune diseases, which often require medical interventions, although LGL leukemia itself is seldom lethal. Immunologic dysregulations in LGL leukemia contribute to the development of complications, for example, neutropenia with the involvement of Fas ligand system and, in pure red cell aplasia, which is a common complication among the patients of East Asian origin, impairing erythroid developments by cytotoxic T cells. Rheumatoid arthritis (RA) is the most prevalent nonhematological consequence, and Felty syndrome, a rare form of RA, and T-LGL leukemia have a lot in common. When patients have LGL leukemia-associated complications, immunosuppressive medication is a mainstay of treatment. Characteristic mutational features in STAT3, STAT5B, CCL22, and other genes in specific subtypes of LGL leukemia have been detected, that would be associated with immunologically mediated molecular pathogenesis in LGL leukemia, and these new findings may help in creating optimal diagnostic approaches or novel therapies for LGL leukemia.