Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma

Curr Opin Hematol. 2017 Jul;24(4):336-344. doi: 10.1097/MOH.0000000000000358.

Abstract

Purpose of review: Next generation sequencing and large-scale analysis of patient specimens has created a more complete picture of multiple myeloma (MM) revealing that epigenetic deregulation is a prominent factor in MM pathogenesis.

Recent findings: Over half of MM patients have mutations in genes encoding epigenetic modifier enzymes. The DNA methylation profile of MM is related to the stage of the disease and certain classes of mutations in epigenetic modifiers are more prevalent upon disease relapse, suggesting a role in disease progression. Many small molecules targeting regulators of epigenetic machinery have been developed and clinical trials are underway for some of these in MM.

Summary: Recent findings suggest that epigenetic targeting drugs could be an important strategy to cure MM. Combining these agents along with other strategies to affect the MM cell such as immunomodulatory drugs and proteasome inhibitors may enhance efficacy of combination regimens in MM.

Publication types

  • Review

MeSH terms

  • Acetylation / drug effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Chromatin Assembly and Disassembly
  • Clinical Trials as Topic
  • DNA Methylation / drug effects
  • Epigenesis, Genetic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Humans
  • Methylation / drug effects
  • Molecular Targeted Therapy
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Mutation*

Substances

  • Antineoplastic Agents
  • Histones
  • Histone-Lysine N-Methyltransferase