Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.

ABSTRACT: Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target

SUBMITTER: Stankov MV 

PROVIDER: S-EPMC3947652 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature