The Novel Class IIa Selective Histone Deacetylase Inhibitor YAK540 Is Synergistic with Bortezomib in Leukemia Cell Lines.

ABSTRACT: The treatment of leukemias, especially acute myeloid leukemia (AML), is still a challenge as can be seen by poor 5-year survival of AML. Therefore, new therapeutic approaches are needed to increase the treatment success. Epigenetic aberrations play a role in pathogenesis and resistance of leukemia. Histone deacetylase (HDAC) inhibitors (HDACIs) can normalize epigenetic disbalance by affecting gene expression. In order to decrease side effects of so far mainly used pan-HDACIs, this paper introduces the novel highly selective class IIa HDACI YAK540. A synergistic cytotoxic effect was observed between YAK540 and the proteasome inhibitor bortezomib (BTZ) as analyzed by the Chou-Talalay method. The combination of YAK540 and BTZ showed generally increased proapoptotic gene expression, increased

SUBMITTER: Bollmann LM 

PROVIDER: S-EPMC9656955 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature