Abstract A189: Expression of fusion proteins in acute myeloid leukemia cells increases sensitivity to histone deacetylase inhibitors

摘要: Acute Myeloid Leukemias (AMLs) are often characterized by chromosomal rearrangements that result in fusion proteins with aberrant transcriptional regulatory activities. These fusion proteins bind to gene promoters and recruit corepressors such as histone deacetylases (HDACs), which remodel chromatin into a closed conformation thereby silencing genes and contributing to a malignant phenotype. Aberrantly silenced genes include tumor suppressor and pro‐differentiation genes. In addition, multiple groups have reported a DNA repair deficient phenotype concurrent with the expression of different fusion proteins in leukemia. Small molecule HDAC inhibitors (HDACi) were devised as a strategy to reverse transcriptional repression. Indeed, many studies have demonstrated the ability of HDACi to re‐sensitize leukemic cells to differentiating stimuli. However, other studies have revealed alternate methods by …