Targeting Epigenetic Modifiers Can Reduce the Clonogenic Capacities of Sézary Cells

Frontiers in Oncology

Marie Beylot-Barry¹  Roland Tomb²  Chantal Farra³  Alain Chebly⁴  Jean-Philippe Merlio⁵  Edith Chevret⁶  Martina Prochazkova-Carlotti⁶  Yamina Idrissi⁶  Laurence Bresson-Bepoldin⁶  Sandrine Poglio⁶ 

[1] Department of Dermatology, Bordeaux University Hospital Center, Bordeaux, France;Department of Dermatology, Hotel-Dieu de France Medical Center, Beirut, Lebanon;Department of Genetics, Hotel-Dieu de France Medical Center, Beirut, Lebanon;Medical Genetics Unit (UGM), Faculty of Medicine, Saint Joseph University, Beirut, Lebanon;Tumor Bank and Tumor Biology Laboratory, Bordeaux University Hospital Center, Pessac, France;Univ. Bordeaux, INSERM U1053, Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France;

关键词: cutaneous T-cell lymphomas (CTCL);    Sezary syndrome (SS);    5-azacytidine;    romidepsin;    vorinostat;    Histone deacetylase inhibitor;   

DOI  :  10.3389/fonc.2021.775253

来源: DOAJ

【 摘 要 】

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphomas (CTCL) in which the human Telomerase Reverse Transcriptase (hTERT) gene is re-expressed. Current available treatments do not provide long-term response. We previously reported that Histone deacetylase inhibitors (HDACi, romidespin and vorinostat) and a DNA methyltransferase inhibitor (DNMTi, 5-azacytidine) can reduce hTERT expression without altering the methylation level of hTERT promoter. Romidepsin and vorinostat are approved for CTCL treatment, while 5-azacytidine is approved for the treatment of several hematological disorders, but not for CTCL. Here, using the soft agar assay, we analyzed the functional effect of the aforementioned epidrugs on the clonogenic capacities of Sézary cells. Our data revealed that, besides hTERT downregulation, epidrugs’ pressure reduced the proliferative and the tumor formation capacities in Sézary cells in vitro.

【 授权许可】

Unknown