Dysfunction of immune system in the development of large granular lymphocyte leukemia.

OBJECTIVES: Large granular lymphocyte (LGL) leukemia is a rare type of lymphoproliferative disease caused by clonal antigenic stimulation of T cells and natural killer (NK) cells.

METHODS: In this review, we focus on the current knowledge of the immunological dysfunctions associated with LGL leukemia and the associated disorders coexistent with this disease. Novel therapeutic options targeting known molecular mechanisms are also discussed.

RESULTS AND DISCUSSION: The pathogenesis of LGL leukemia involves the accumulation of gene mutations, dysregulated signaling pathways and immunological dysfunction. Mounting evidence indicated that dysregulated survival signaling pathways may be responsible for the immunological dysfunction in LGL leukemia including decreased numbers of neutrophils, dysregulated signal transduction of NK cells, abnormal B-cells, aberrant CD8+ T cells, as well as autoimmune and hematological abnormalities.

CONCLUSION: A better understanding of the immune dysregulation triggered by LGL leukemia will be beneficial to explore the pathogenesis and potential therapeutic targets for this disease.