Journal of Blood Disorders & Transfusion

Understanding the epigenetic response in resistant cancer cells to romidepsin therapy

7^th World Hematologists Congress

May 08-09, 2017 Barcelona, Spain

Ellen McAuley

University of Liverpool, UK

Posters & Accepted Abstracts: J Blood Disord Transfus

Abstract:

The histone deacetylase inhibitor (HDACi) romidepsin has shown therapeutic potential in the treatment of peripheral and cutaneous T cell lymphoma although resistance to this novel therapeutic agent often develops. Multiple mechanisms of resistance to HDACis have been identified in vitro, but how this class of epigenetic inhibitors manipulates the epigenome and whether this is altered to cause development of tolerance in cancer cells has not been studied. Previous work in the department into HDACi resistance has identified candidate epigenetic genes, including HDAC8 and KDM5A, whose mRNA expression pattern is perturbed in response to HDACi treatment in multiple romidepsin resistant cell lines. However, whether these alterations in mRNA levels reflect protein expression and functional changes remains unclear. Using the CTCL cell line HuT78 and its romidepsin resistant counterpart (RHuT78), it was shown that both HDAC8 and the KDM5A protein expression are altered differently between the wild type and the resistant cell line upon treatment with romidepsin. Furthermore, by combining romidepsin treatment with the DNA methyltransferase inhibitor 5-azacytidine and inducing an apoptotic response in RHuT78 cells, the expression changes of HDAC8 and KDM5A could be transformed back to that seen in the parental HuT78 cell line. These results suggest that both HDAC8 and KDM5A may contribute towards defining resistant responses to HDACis and are therefore worthy for further study into potential therapeutic targets for inhibition to overcome resistance to romidepsin.

Biography :

Email: ellenfmcauley@gmail.com