Large granular lymphocyte (LGL) leukemia is a chronic hematological disease, in which the diseased cells consist of clonal large, mature T or NK cells. Major symptoms and findings of the disease include anemia, neutropenia and rheumatoid arthritis. Immunosuppressive treatments, such as methotrexate, usually relieve the symptoms in patients. In LGL leukemia, next-generation sequencing has recently revealed mutations in the STAT3 and STAT5B genes that lead to the activation of these proteins. Similar mutations have been detected in hereditary autoimmune diseases, disorders of bone marrow and malignancies of lymphocyte origin.