Are inhibitors of histone deacetylase 8 (HDAC8) effective in hematological cancers especially acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)?

Eur J Med Chem. 2023 Oct 5:258:115594. doi: 10.1016/j.ejmech.2023.115594. Epub 2023 Jun 25.

Abstract

Histone deacetylase 8 (HDAC8) aberrantly deacetylates histone and non-histone proteins. These include structural maintenance of chromosome 3 (SMC3) cohesin protein, retinoic acid induced 1 (RAI1), p53, etc and thus, regulating diverse processes such as leukemic stem cell (LSC) transformation and maintenance. HDAC8, one of the crucial HDACs, affects the gene silencing process in solid and hematological cancer progressions especially on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A specific HDAC8 inhibitor PCI-34051 showed promising results against both T-cell lymphoma and AML. Here, we summarize the role of HDAC8 in hematological malignancies, especially in AML and ALL. This article also introduces the structure/function of HDAC8 and a special attention has been paid to address the HDAC8 enzyme selectivity issue in hematological cancer especially against AML and ALL.

Keywords: Cancer; Enzyme selectivity; HDAC; HDAC8 inhibitor; Hematological malignancy.

Publication types

  • Review

MeSH terms

  • Hematologic Neoplasms*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Deacetylases / metabolism
  • Humans
  • Leukemia, Myeloid, Acute* / pathology
  • Percutaneous Coronary Intervention*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Repressor Proteins

Substances

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • HDAC8 protein, human
  • Repressor Proteins