Differentiation of myeloid leukemia cells by HDAC-inhibitors

Histone deacetylase (HDAC)-inhibitors are a new class of promising anti-cancer agents. Here we show that different structural classes of HDAC-inhibitors (butyric acid, apicidin, MS-275, SAHA, novel synthesized valproic acid derivatives) exhibit anti-proliferative and erythroid differentiation inducing activities in bcr/abl positive K562 myeloid leukemia cells. Inhibition of cell proliferation and erythroid differentiation are accompanied by induction of p21 mRNA and accumulation of hyperacetylated histone H4 proteins in cells. We identified a K562 subline with resistance to erythroid differentiation by HDAC-inhi…