The JAK/STAT signaling pathway and its main oncogenic alterations in primary mediastinal large B-cell lymphoma. On the left, the JAK tyrosine kinases are activated by cytokines and phosphorylate the signal transducers and activators of transcription (STATs), which subsequently dimerize and translocate to the nucleus where they promote the transcription of target genes. One of these genes is the suppressor of cytokine signaling 1 (SOCS1) that inhibits the pathway in an autoregulatory loop by binding to the phosphorylated JAK and promoting its degradation through the proteasome pathway. On the right, PMBL carries 2 putative oncogenic aberrations in the JAK2/STAT pathway.JAK2is amplified and overexpressed and the protein is phosphorylated. Prolonged JAK2 half-life is sustained bySOCS1mutations. Expression profiling of PMBL has detected overexpression of the IL-4/IL-13 receptor, JAK2 and STAT, and several target genes of this pathway.