The Role of Histones Proteins in Hematological Neoplasias

Abstract

The basic unit of chromatin is the nucleosome, consisting of approximately 146 DNA base pairs wrapped around a core octamer of proteins known as histones. These basic proteins were initially regarded as merely structural components but are now recognized for their important role in maintaining the dynamic equilibrium of chromatin. The amino terminal tails of histones are susceptible to a variety of post-translational modifications, like methylation, acetylation, phosphorylation, and others, which regulate their functions. Some modifications are generally associated with active genes, whereas others are associated with repressed genes. Currently one of the most widely studied modifications is acetylation, which depends on two families of enzymes, histone acetyltransferases (HAT) and histone deacetylases (HDAC). The chromosomal mutations or translocations involving HAT and HDAC genes result in hematological malignancies such as acute promyelocytic leukemia, lymphoma, and others. Histone deacetylase inhibitors (HDACI) have appeared as a new class of anticancer agents. HDACI have shown activity against various types of cancer and notable effects on tumor cell proliferation, programmed cell death, differentiation, and angiogenesis in vitro and in vivo.