Histone acetylation: novel target for the treatment of acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) has been generally considered a genetic disease (disorder) with an aggressive tumor entity of highly proliferative malignant lymphoid cells. However, in recent years, significant advances have been made in the elucidation of the ALL-associated processes. Thus, we understand that histone acetylation is involved in the permanent changes of gene expression controlling ALL developmental outcomes. In this article, we will focus on histone acetylation associated with ALL, their implications as biomarkers for prognostic, and their preclinical and clinical applications.

An epigenetic view of developmental diseases: new targets, new therapies

“…[6] Further, multiple small molecule inhibitors targeting on histone modification machinery including histone methyltransferase (HMT) and demethyltransferase (HDM), histone acetyltransferase (HAT) and histone deacetylase (HDAC) have also been identified. [6,7] Although many challenges have to be dealt with and the potential compounds need to be further studied in detail, epigenetic based treatments would hold great promise in combination with the conventional therapeutic methods.…”

Cancer Treatment: An Epigenetic View

“…HDAC enzymes are responsible to remove acetyl groups during deacetylation, and allows histones to interact with DNA, which means silencing of gene transcription. 40 Histone acetylation and deacetylation changes the activity of histones. Histone acetylation is effective during the regulation of gene expression, and HDAC inhibitors are altered the transcription of a small number of genes, and leads to growth arrest, differentiation, and/or apoptosis of many tumor cells.…”

“…Histone acetylation is effective during the regulation of gene expression, and HDAC inhibitors are altered the transcription of a small number of genes, and leads to growth arrest, differentiation, and/or apoptosis of many tumor cells. 40 Changes in histone acetylation can contribute to carcinogenesis. 40 This makes as powerful anticancer agents of HDACs to restore normal histone acetylation status of cells to enhance gene transcription.…”

Retinoic Acid Receptors in Acute Myeloid Leukemia Therapy

“…Upon interaction with ETO, the N-CoR/SMRT/HDAC complex contributes to repression of genes that regulate hematopoietic precursors and terminal myeloid differentiation [81,82] Regulation of HAT and HDAC enzymes is crucial for gene transcription. HATs are among the most frequently mutated genes in urothelial carcinomas and upregulation of HDACs has been noted in a wide variety of cancers [83,84]. In particular, several HDACs have been found to be upregulated in acute lymphoblastic leukemia (ALL) and are associated with a poor prognosis.…”