Validating the genetic alterations in cutaneous T-cell lymphoma: unraveling the role of SOCS1 and HNRNPK through genetically engineered mouse models

Abstract

This dissertation investigates the genetic drivers of Cutaneous T-cell Lymphoma (CTCL) using advanced in vivo mouse models. CTCL is a rare type of non-Hodgkin lymphoma affecting the skin. The study aims to understand how genetic alterations, specifically in SOCS1 and HNRNPK, contribute to CTCL's development. Key findings include the role of SOCS1 in disease progression, where SOCS1 mono-allelic loss in skin-resident CD4+ T cells leads to early signs of mycosis fungoides (MF) in a chronic inflammation setting. HNRNPK deletion in CD4+ T cells further models early-stage CTCL, demonstrating chronic skin inflammation and CD4+ cell infiltration. These genetically engineered mouse models provide critical insights into the pathogenesis of CTCL and its early-stage mechanisms. Overall, the thesis contributes to understanding the genetic foundations of CTCL and highlights the potential for targeted therapies. Future research could further refine these models, offering improved strategies for studying and treating CTCL.