To address the role of DOT1L in the therapeutic effect of HDAC inhibitors, we here studied single and combination treatments of two CTCL cell lines with the HDAC Class I, II and IV inhibitors Vorinostat (SAHA) and Panobinostat, both of which show promising results in CTCL treatment (Mann et al., 2007; Ellis et al., 2008; Duvic et al., 2013; Barbarotta and Hurley, 2015; Jones et al., 2016; Lopez et al., 2018; Sermer et al., 2019; Chen et al., 2020; Lai and Wang, 2021b; Pavlidis et al., 2021), and the highly specific and clinically relevant DOT1L inhibitors Pinometostat and SGC-0946. The gene discussed is DOT1L; the disease is primary cutaneous T-cell non-Hodgkin lymphoma.