HDAC1 acts as a tumor suppressor in ALK-positive anaplastic
large cell lymphoma: implications for HDAC inhibitor therapy

J 2025

HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy

ZRIMSEK, Masa; Kristina DRAGANIC; Anna MALZER; Verena DOBLMAYR; Katarina MISURA et al.

Základní údaje

Originální název

HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy

Autoři

Vydání

Leukemia, LONDON, SPRINGERNATURE, 2025, 0887-6924

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.400 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

ALK-positive anaplastic large cell lymphoma; HDAC1; tumor suppressor; HDAC inhibitors; epigenetic regulation

Štítky

14110323, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 2. 2026 09:23, Mgr. Tereza Miškechová

Anotace

V originále

Histone deacetylases (HDACs) are frequently deregulated in cancer, and several HDAC inhibitors (HDACi) have gained approval for treating peripheral T cell lymphomas. Here, we investigated the effects of pharmacological or genetic HDAC inhibition on NPM::ALK positive anaplastic large cell lymphoma (ALCL) development to assess the potential use of HDACi for the treatment of this disease. Short-term systemic pharmacological inhibition of HDACs using the HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM::ALK fusion oncogene. To further disentangle the effects of systemic HDAC inhibition from thymocyte intrinsic effects, conditional genetic deletions of HDAC1 and HDAC2 enzymes were employed. In sharp contrast, T cell-specific deletion of Hdac1 or Hdac2 in the ALCL mouse model significantly accelerated NPM::ALK-driven lymphomagenesis, with Hdac1 loss having a more pronounced effect. Integration of gene expression and chromatin accessibility data revealed that Hdac1 deletion selectively perturbed cell type-specific transcriptional programs, crucial for T cell differentiation and signaling. Moreover, multiple oncogenic signaling pathways, including PDGFRB signaling, were highly upregulated. Our findings underscore the tumor-suppressive function of HDAC1 and HDAC2 in T cells during ALCL development. Nevertheless, systemic pharmacological inhibition of HDACs could still potentially improve current therapeutic outcomes.

Citovat

ZRIMSEK, Masa; Kristina DRAGANIC; Anna MALZER; Verena DOBLMAYR; Katarina MISURA; de Freitas E Silva RAFAEL; Jamie D MATTHEWS; Fabio IANNELLI; Sabrina WOHLHAUPTER; Carlos Uziel Perez MALLA; Heinz FISCHER; Helga SCHACHNER; Ana-Iris SCHIEFER; Raheleh SHEIBANI-TEZERJI; Roberto CHIARLE; Suzanne Dawn TURNER; Wilfried ELLMEIER; Christian SEISER a Gerda EGGER. HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy. Leukemia. LONDON: SPRINGERNATURE, 2025, roč. 39, č. 6, s. 1412-1424. ISSN 0887-6924. Dostupné z: https://doi.org/10.1038/s41375-025-02584-9.

@article{2494898,
   author = {Zrimsek, Masa and Draganic, Kristina and Malzer, Anna and Doblmayr, Verena and Misura, Katarina and Rafael, de Freitas E Silva and Matthews, Jamie D and Iannelli, Fabio and Wohlhaupter, Sabrina and Malla, Carlos Uziel Perez and Fischer, Heinz and Schachner, Helga and Schiefer, AnaandIris and SheibaniandTezerji, Raheleh and Chiarle, Roberto and Turner, Suzanne Dawn and Ellmeier, Wilfried and Seiser, Christian and Egger, Gerda},
   article_location = {LONDON},
   article_number = {6},
   doi = {https://doi.org/10.1038/s41375-025-02584-9},
   keywords = {ALK-positive anaplastic large cell lymphoma; HDAC1; tumor suppressor; HDAC inhibitors; epigenetic regulation},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy},
   url = {https://www.nature.com/articles/s41375-025-02584-9},
   volume = {39},
   year = {2025}
}

TY  - JOUR
ID  - 2494898
AU  - Zrimsek, Masa - Draganic, Kristina - Malzer, Anna - Doblmayr, Verena - Misura, Katarina - Rafael, de Freitas E Silva - Matthews, Jamie D - Iannelli, Fabio - Wohlhaupter, Sabrina - Malla, Carlos Uziel Perez - Fischer, Heinz - Schachner, Helga - Schiefer, Ana-Iris - Sheibani-Tezerji, Raheleh - Chiarle, Roberto - Turner, Suzanne Dawn - Ellmeier, Wilfried - Seiser, Christian - Egger, Gerda
PY  - 2025
TI  - HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy
JF  - Leukemia
VL  - 39
IS  - 6
SP  - 1412-1424
EP  - 1412-1424
PB  - SPRINGERNATURE
SN  - 08876924
KW  - ALK-positive anaplastic large cell lymphoma
KW  - HDAC1
KW  - tumor suppressor
KW  - HDAC inhibitors
KW  - epigenetic regulation
UR  - https://www.nature.com/articles/s41375-025-02584-9
N2  - Histone deacetylases (HDACs) are frequently deregulated in cancer, and several HDAC inhibitors (HDACi) have gained approval for treating peripheral T cell lymphomas. Here, we investigated the effects of pharmacological or genetic HDAC inhibition on NPM::ALK positive anaplastic large cell lymphoma (ALCL) development to assess the potential use of HDACi for the treatment of this disease. Short-term systemic pharmacological inhibition of HDACs using the HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM::ALK fusion oncogene. To further disentangle the effects of systemic HDAC inhibition from thymocyte intrinsic effects, conditional genetic deletions of HDAC1 and HDAC2 enzymes were employed. In sharp contrast, T cell-specific deletion of Hdac1 or Hdac2 in the ALCL mouse model significantly accelerated NPM::ALK-driven lymphomagenesis, with Hdac1 loss having a more pronounced effect. Integration of gene expression and chromatin accessibility data revealed that Hdac1 deletion selectively perturbed cell type-specific transcriptional programs, crucial for T cell differentiation and signaling. Moreover, multiple oncogenic signaling pathways, including PDGFRB signaling, were highly upregulated. Our findings underscore the tumor-suppressive function of HDAC1 and HDAC2 in T cells during ALCL development. Nevertheless, systemic pharmacological inhibition of HDACs could still potentially improve current therapeutic outcomes.
ER  -

ZRIMSEK, Masa; Kristina DRAGANIC; Anna MALZER; Verena DOBLMAYR; Katarina MISURA; de Freitas E Silva RAFAEL; Jamie D MATTHEWS; Fabio IANNELLI; Sabrina WOHLHAUPTER; Carlos Uziel Perez MALLA; Heinz FISCHER; Helga SCHACHNER; Ana-Iris SCHIEFER; Raheleh SHEIBANI-TEZERJI; Roberto CHIARLE; Suzanne Dawn TURNER; Wilfried ELLMEIER; Christian SEISER a Gerda EGGER. HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy. \textit{Leukemia}. LONDON: SPRINGERNATURE, 2025, roč.~39, č.~6, s.~1412-1424. ISSN~0887-6924. Dostupné z: https://doi.org/10.1038/s41375-025-02584-9.

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