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New, particular STAT3 inhibitors 29 possess recently been evaluated in early clinical trials for the treatment of other hematologic cancers, and our results claim that preclinical and medical studies of these drugs are also warranted in patients with huge granular lymphocytic leukemia. The diagnosis of large granular lymphocytic leukemia could be difficult to establish, since benign large granular lymphocytosis with clonal T cells might occur together with viral infections or autoimmune disorders. Somatic STAT3 mutations might provide a diagnostic device for classifying some situations of large granular lymphocytosis as true T-cell leukemias that are distinct from clonally skewed reactive processes and from hyperreactive or persistent T-cell responses.