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Ocio endnote software9/7/2023 ![]() Plasmacytoid dendritic cells (pDCs) were identified as the cells producing type I IFN in response to panobinostat, through transcriptional activation of IFN genes concomitant with increased H3K27 acetylation at these loci. In a genetically engineered model of t(8 21) AML, leukemia cell differentiation and therapeutic benefit mediated by the HDAC inhibitor panobinostat required activation of the type I interferon (IFN) signaling pathway. Here we discovered a novel mechanism of immune regulation through the inhibition of histone deacetylases (HDACs). While these agents can affect tumor cell growth and proliferation, recent studies have demonstrated that pharmacological de-regulation of epigenetic modifiers may additionally mediate anti-tumor immune responses. Pharmacological inhibition of epigenetic enzymes can have therapeutic benefit, particularly against hematological malignancies.
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