Epimutational profile of hematologic malignancies as attractive target for new epigenetic therapies

Oncotarget. 2016 Aug 30;7(35):57327-57350. doi: 10.18632/oncotarget.10033.

Abstract

In recent years, recurrent somatic mutations in epigenetic regulators have been identified in patients with hematological malignancies. Furthermore, chromosomal translocations in which the fusion protein partners are themselves epigenetic regulators or where epigenetic regulators are recruited/targeted by oncogenic fusion proteins have also been described. Evidence has accumulated showing that "epigenetic drugs" are likely to provide clinical benefits in several hematological malignancies, granting their approval for the treatment of myelodysplastic syndromes and cutaneous T-cell lymphomas. A large number of pre-clinical and clinical trials evaluating epigenetic drugs alone or in combination therapies are ongoing. The aim of this review is to provide a comprehensive summary of known epigenetic alterations and of the current use of epigenetic drugs for the treatment of hematological malignancies.

Keywords: 5-aza-2’-deoxycytidine; DNA methylation; azacytidine; hematological malignancies; histone modifications.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Antineoplastic Agents / therapeutic use
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • DNA Methylation
  • Decitabine
  • Epigenesis, Genetic*
  • Female
  • Hematologic Neoplasms / genetics*
  • Histones / chemistry
  • Humans
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Lymphoma, T-Cell, Cutaneous / therapy
  • Male
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / therapy
  • Protein Domains

Substances

  • Antineoplastic Agents
  • Histones
  • Decitabine
  • Azacitidine