Overall, considering such losses of negative regulators and the GOF mutations in <i>JAK</i> and <i>STAT</i> genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity.
Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas.
These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL.