Recently, the pathophysiological mechanism of LGL leukemia was outstandingly improved with the recent identification of acquired mutations of the SH2 domain of STAT3 and STAT5b in 40% and 2% of cases, respectively [26], [40], and the search for these mutations may help to distinguish LGL leukemia from reactive CD8+ T-cell expansions. This evidence concerns the gene STAT5B and T-cell large granular lymphocyte leukemia.