Activity of the histone deacetylase inhibitors LBH589 and LAQ824 in hematologic malignancies

Histone deacetylase (HDAC) inhibitors (HDIs) are potent inducers of in vitro growth arrest, differentiation and apoptosis of human leukemia and lymphoma cells as well as exert in vivo anti-leukemia and anti-lymphoma effects. The hydroxamic acid (HA) analogue class of HDIs, e.g., LBH589 and LAQ824, have been shown to induce not only the acetylation of the lysine residues of core nucleosomal histones but also of transcription factors and other important proteins. Thus, they should be referred to as protein deacetylases. Together, HA-HDI-induced modifications of proteins mediate the biologic the therapeutic effects, which are currently being investigated through pre-clinical and clinical studies in hematologic malignancies. This review briefly describes the current status of the development of these agents in the therapy of hematologic malignancies.