Role of Histone Deacetylase Inhibitors in Leukemia Therapy

Abstract

Histone deacetylases (HDACs) are enzymes responsible for the deacetylation of both histone and non-histone substrates. They significantly impact gene expression by interfering with fusion genes and transcription factors, leading to the proliferation and migration of cancerous cells while inhibiting apoptosis through tumor suppressor genes. Evaluating the overexpression of HDACs in leukemias could offer a novel diagnostic strategy and reveal new therapeutic targets. Histone deacetylase inhibitors (HDACi) may reverse the activation of tumor suppressor genes (TSG), thus reducing the viability and malignant growth of tumor cells. A novel approach in HDACi designs involves the simultaneous inhi-bition of protein kinases and HDACs within a single molecule. The effectiveness of structurally varied compounds as HDAC inhibitors indicates that their mechanism of action might extend beyond merely obstructing the catalytic site, potentially involving interactions with the enzyme's rim and other proteins, independent of deacetylase activity. The efficacy of HDACi treatment has been validated in multiple clinical studies. Advancements in the discovery of new HDIs that target various cellular pathways could lead to innovative treatment options and improved survival rates for patients. This review focuses on the role of HDACs as therapeutic targets in different leukemia types.