The emerging role of GSK‐3β in the pathobiology of classical Hodgkin lymphoma

• DOI: 10.1111/his.13189
• Publication Date: 2017-02-17T00:32:42Z
• Authors: Claudio Agostinelli; Silvia Carloni; Francesco Limarzi; Simona Righi; Maria Antonella L...; Gerardo Musuraca; Michelangelo Fior...; Roberta Napolitano; Antonio Cuneo; Daniele Vergara; Pier Luigi Zinzani; Elena Sabattini; Stefano A Pileri; Serena De Matteis
• Keywords: GSK-3β; Hodgkin; β-catenin; Gene Expression Regulation, Neoplastic; 0301 basic medicine; GSK-3β; Hodgkin; β-catenin; 2734; Histology; 03 medical and health sciences; Glycogen Synthase Kinase 3 beta; Humans; Transcriptome; Hodgkin Disease

Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, survival and cellular senescence. Its main biological function to inhibit β-catenin by sequestration promotion of its proteasomal degradation the Wnt canonical pathway; however, GSK-3β interacts with multiple signalling pathways, aberrant expression enzyme was reported many solid neoplasms. This study aimed investigate relevance classical Hodgkin lymphomas (cHL).We analysed functional status cHL using antibodies raised against fixation-resistant epitopes phospho Y216 (active form), S9 (inactive form) protein. We first detected pY216 active form 100 (100%) cases, line latter profile, protein found only 12 (12%) samples. As previously bladder cancer, pancreatic adenocarcinoma chronic lymphocytic leukaemia, we showed an nuclear localization neoplastic clone 78 (78%) cases.We demonstrated activation resulting inhibition Wnt/β-catenin signal cascade accumulation activated nuclei Reed-Sternberg cells. These findings may be relevant for future clinical studies, identifying as potential therapeutic target cHL.