HDAC10 and its implications in Sézary syndrome pathogenesis
Cutaneous T-cell lymphomas (CTCL) are a group of rare hematological malignancies characterized by infiltration of malignant T-cells into the skin. Two main types of CTCL constitute of Mycosis Fungoides (MF), a more indolent form of the disease, and Sézary syndrome (SS), the aggressive and leukemic v...
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Frontiers Media S.A.
2025-01-01
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| author | Monika Pieniawska Karolina Rassek Bogumiła Skwara Magdalena Żurawek Iwona Ziółkowska-Suchanek Lydia Visser Monique Lodewijk Małgorzata Sokołowska-Wojdyło Małgorzata Sokołowska-Wojdyło Berenika Olszewska Roman J. Nowicki Roman J. Nowicki Tomasz Stein Aleksandra Dańczak-Pazdrowska Adriana Polańska Marta Szymoniak-Lipska Natalia Rozwadowska Katarzyna Iżykowska |
| author_facet | Monika Pieniawska Karolina Rassek Bogumiła Skwara Magdalena Żurawek Iwona Ziółkowska-Suchanek Lydia Visser Monique Lodewijk Małgorzata Sokołowska-Wojdyło Małgorzata Sokołowska-Wojdyło Berenika Olszewska Roman J. Nowicki Roman J. Nowicki Tomasz Stein Aleksandra Dańczak-Pazdrowska Adriana Polańska Marta Szymoniak-Lipska Natalia Rozwadowska Katarzyna Iżykowska |
| author_sort | Monika Pieniawska |
| collection | DOAJ |
| description | Cutaneous T-cell lymphomas (CTCL) are a group of rare hematological malignancies characterized by infiltration of malignant T-cells into the skin. Two main types of CTCL constitute of Mycosis Fungoides (MF), a more indolent form of the disease, and Sézary syndrome (SS), the aggressive and leukemic variant with blood involvement. Sézary syndrome presents a significant clinical challenge due to its very aggressive nature, poor prognosis, and treatment resistance, and to date, the disease remains incurable. Histone deacetylase inhibitors have gained attention in CTCL treatment with promising results, but they expose limited specificity and strong side effects. Recent genomic studies underscore the role of epigenetic modifiers in CTCL pathogenesis, prompting an investigation into HDAC10, a member of class IIb HDACs, in SS. HDAC10 was investigated in different cancers, revealing its involvement in cell cycle regulation, apoptosis, and autophagy, but its role in CTCL is unknown. In this study we aimed to determine the role of HDAC10 in SS, focusing on its cellular localization, role in cell growth, and therapeutic potential. We indicated that HDAC10 is overexpressed in SS patients and located mainly in the cytoplasm. Its overexpression leads to an inhibitory effect on apoptosis progression when exposed to the pro-apoptotic compound Camptothecin (CPT). Knockdown of HDAC10 resulted in reduced cell growth and induction of apoptosis and autophagy, highlighting its potential importance in CTCL pathogenesis. Whole transcriptome analysis indicated that HDAC10 is associated with crucial cancer-related pathways, for example, hematopoietic cell lineage, PI3K-Akt signaling pathway, Ras signaling pathway, MAPK signaling pathway or JAK-STAT signaling pathway, which are critical for the survival and proliferation of malignant T cells. Inhibition of HDAC10 with selective HDAC10i increased the sensitivity of Sézary cells to the pro-apoptotic CPT. Our findings demonstrate that HDAC10 plays a key role in the molecular background of Sézary syndrome, highlighting its importance in the cellular mechanisms of the disease. |
| format | Article |
| id | doaj-art-6aa8c3f7c5ae4b01889f5f4493200c17 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-6aa8c3f7c5ae4b01889f5f4493200c172025-01-31T06:40:10ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.14801921480192HDAC10 and its implications in Sézary syndrome pathogenesisMonika Pieniawska0Karolina Rassek1Bogumiła Skwara2Magdalena Żurawek3Iwona Ziółkowska-Suchanek4Lydia Visser5Monique Lodewijk6Małgorzata Sokołowska-Wojdyło7Małgorzata Sokołowska-Wojdyło8Berenika Olszewska9Roman J. Nowicki10Roman J. Nowicki11Tomasz Stein12Aleksandra Dańczak-Pazdrowska13Adriana Polańska14Marta Szymoniak-Lipska15Natalia Rozwadowska16Katarzyna Iżykowska17Institute of Human Genetics, Polish Academy of Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, PolandDepartment of Dermatology, Venereology and Allergology, University Clinical Centre, Gdańsk, PolandDepartment of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, PolandDepartment of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, PolandDepartment of Dermatology, Venereology and Allergology, University Clinical Centre, Gdańsk, PolandDepartment of Dermatology, Poznań University of Medical Sciences, Poznań, PolandDepartment of Dermatology, Poznań University of Medical Sciences, Poznań, PolandDepartment of Dermatology and Venereology, Poznań University of Medical Sciences, Poznań, PolandDepartment of Dermatology, Poznań University of Medical Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznań, PolandCutaneous T-cell lymphomas (CTCL) are a group of rare hematological malignancies characterized by infiltration of malignant T-cells into the skin. Two main types of CTCL constitute of Mycosis Fungoides (MF), a more indolent form of the disease, and Sézary syndrome (SS), the aggressive and leukemic variant with blood involvement. Sézary syndrome presents a significant clinical challenge due to its very aggressive nature, poor prognosis, and treatment resistance, and to date, the disease remains incurable. Histone deacetylase inhibitors have gained attention in CTCL treatment with promising results, but they expose limited specificity and strong side effects. Recent genomic studies underscore the role of epigenetic modifiers in CTCL pathogenesis, prompting an investigation into HDAC10, a member of class IIb HDACs, in SS. HDAC10 was investigated in different cancers, revealing its involvement in cell cycle regulation, apoptosis, and autophagy, but its role in CTCL is unknown. In this study we aimed to determine the role of HDAC10 in SS, focusing on its cellular localization, role in cell growth, and therapeutic potential. We indicated that HDAC10 is overexpressed in SS patients and located mainly in the cytoplasm. Its overexpression leads to an inhibitory effect on apoptosis progression when exposed to the pro-apoptotic compound Camptothecin (CPT). Knockdown of HDAC10 resulted in reduced cell growth and induction of apoptosis and autophagy, highlighting its potential importance in CTCL pathogenesis. Whole transcriptome analysis indicated that HDAC10 is associated with crucial cancer-related pathways, for example, hematopoietic cell lineage, PI3K-Akt signaling pathway, Ras signaling pathway, MAPK signaling pathway or JAK-STAT signaling pathway, which are critical for the survival and proliferation of malignant T cells. Inhibition of HDAC10 with selective HDAC10i increased the sensitivity of Sézary cells to the pro-apoptotic CPT. Our findings demonstrate that HDAC10 plays a key role in the molecular background of Sézary syndrome, highlighting its importance in the cellular mechanisms of the disease.https://www.frontiersin.org/articles/10.3389/fcell.2025.1480192/fullHDAC10Sézary syndromeCTCLhistone deacetylasesepigenetic regulators |
| spellingShingle | Monika Pieniawska Karolina Rassek Bogumiła Skwara Magdalena Żurawek Iwona Ziółkowska-Suchanek Lydia Visser Monique Lodewijk Małgorzata Sokołowska-Wojdyło Małgorzata Sokołowska-Wojdyło Berenika Olszewska Roman J. Nowicki Roman J. Nowicki Tomasz Stein Aleksandra Dańczak-Pazdrowska Adriana Polańska Marta Szymoniak-Lipska Natalia Rozwadowska Katarzyna Iżykowska HDAC10 and its implications in Sézary syndrome pathogenesis Frontiers in Cell and Developmental Biology HDAC10 Sézary syndrome CTCL histone deacetylases epigenetic regulators |
| title | HDAC10 and its implications in Sézary syndrome pathogenesis |
| title_full | HDAC10 and its implications in Sézary syndrome pathogenesis |
| title_fullStr | HDAC10 and its implications in Sézary syndrome pathogenesis |
| title_full_unstemmed | HDAC10 and its implications in Sézary syndrome pathogenesis |
| title_short | HDAC10 and its implications in Sézary syndrome pathogenesis |
| title_sort | hdac10 and its implications in sezary syndrome pathogenesis |
| topic | HDAC10 Sézary syndrome CTCL histone deacetylases epigenetic regulators |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1480192/full |
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