Leiden University Scholarly Publications

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Luo, Y. (2024)

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

Doctoral Thesis
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...Show moreThis 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.Show less
Cutaneous T- cell lymphoma
Mycosis fungoides
In vivo
CD4 T cells
SOCS1
HNRNPK
All authors
Luo, Y.
Supervisor
Vermeer, M.H.
Co-supervisor
Tensen, C.P.; Gruijl, F.R. de
Committee
Doorn, R. van; Hall, T. van; Bekkenk, M.W.; Derksen, P.W.B.; Visser, K.E. de
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2024-11-12
ISBN (print)
9789074013192