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Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma

Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durab...

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Main Authors: Özistanbullu, Deniz (Author) , Wilhelm, Raphael (Author) , Reichenbach, Gabi (Author) , Doll, Monika (Author) , Bahrami, Karola (Author) , Zöller, Nadja (Author) , Schnütgen, Frank (Author) , König, Anke (Author) , Scheller, Theresia (Author) , Winkler, Lars (Author) , Spahn, Pascal (Author) , Jäger, Manuel (Author) , Nicolay, Jan Peter (Author) , Pfeilschifter, Josef (Author) , Schilling, Bastian (Author) , Kaufmann, Roland (Author) , Koch, Alexander (Author) , Kippenberger, Stefan (Author) , Kleemann, Johannes (Author) , Meissner, Markus (Author)
Format: Article (Journal)
Language:English
Published: June 10 2025
In: Blood advances
Year: 2025, Volume: 9, Issue: 11, Pages: 2651-2662
ISSN:2473-9537
DOI:10.1182/bloodadvances.2024015132
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2024015132
Verlag, lizenzpflichtig, Volltext: https://ashpublications.org/bloodadvances/article/9/11/2651/535799/Estrogen-receptor-stimulation-as-a-possible-novel
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Author Notes:Deniz Özistanbullu, Raphael Wilhelm, Gabi Reichenbach, Monika Doll, Karola Bahrami, Nadja Zöller, Frank Schnütgen, Anke König, Theresia Scheller, Lars Winkler, Pascal Spahn, Manuel Jäger, Jan P. Nicolay, Josef Pfeilschifter, Bastian Schilling, Roland Kaufmann, Alexander Koch, Stefan Kippenberger, Johannes Kleemann, and Markus Meissner
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Summary:Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. Similar to other non-Hodgkin lymphomas (NHLs), MF and SS have a greater incidence rate in males than females. The endocrine contribution to this sex difference is unknown. Although several studies could show a potential role of estrogen receptor β (ERβ) on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing noncancerous skin cells. Liquid chromatography with tandem mass spectrometry analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 than normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly Monomethyl auristatin E. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications.
Item Description:Online veröffentlicht: 28. Mai 2025
Gesehen am 16.09.2025
Physical Description:Online Resource
ISSN:2473-9537
DOI:10.1182/bloodadvances.2024015132

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