<i>STAT3</i> Mutation Is Associated with STAT3 Activation in CD30⁺ ALK⁻ ALCL

• Main Authors: Emma I. Andersson, Oscar Brück, Till Braun, Susanna Mannisto, Leena Saikko, Sonja Lagström, Pekka Ellonen, Sirpa Leppä, Marco Herling, Panu E. Kovanen, Satu Mustjoki
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Cancers
• Subjects: lymphoma; t-cells; stat3; rhoa; ngs
• Online Access: https://www.mdpi.com/2072-6694/12/3/702

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 <i>STAT</i> gene mutations. Patient samples from AITL (<i>n</i> = 30), ALCL (<i>n</i> = 21) and PTCL-NOS (<i>n</i> = 12) cases were sequenced for <i>STAT3</i>, <i>STAT5B, JAK1, JAK3,</i> and <i>RHOA</i> mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered <i>STAT3</i> mutations in 13% of AITL, 13% of ALK⁺ ALCL, 38% of ALK^&#8722; ALCL and 17% of PTCL-NOS cases. However, no <i>STAT5B</i> mutations were found and <i>JAK</i> mutations were only present in ALK^- ALCL (15%). Concurrent mutations were found in all subgroups except ALK⁺ ALCL where <i>STAT3</i> 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 <i>JAK1</i> or <i>STAT3</i> mutations and CD30⁺ phenotype representing primarily ALK^&#8722; ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.