Mutation Is Associated with STAT3 Activation in CD30 ALK ALCL.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of gene mutations. Patient samples from AITL ( = 30), ALCL ( = 21) and PTCL-NOS ( = 12) cases were sequenced for , and mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered mutations in 13% of AITL, 13% of ALK ALCL, 38% of ALK ALCL and 17% of PTCL-NOS cases. However, no mutations were found and mutations were only present in ALK ALCL (15%). Concurrent mutations were found in all subgroups except ALK ALCL where mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either or mutations and CD30 phenotype representing primarily ALK ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.