Mechanisms of epigenetic regulation of leukemia onset and progression

Adv Immunol. 2013:117:1-38. doi: 10.1016/B978-0-12-410524-9.00001-3.

Abstract

Over the past decade, it has become clear that both genetics and epigenetics play pivotal roles in cancer onset and progression. The importance of epigenetic regulation in proper maintenance of cellular state is highlighted by the frequent mutation of chromatin modulating factors across cancer subtypes. Identification of these mutations has created an interest in designing drugs that target enzymes involved in DNA methylation and posttranslational modification of histones. In this review, we discuss recurrent genetic alterations to epigenetic modulators in both myeloid and lymphoid leukemias. Furthermore, we review how these perturbations contribute to leukemogenesis and impact disease outcome and treatment efficacy. Finally, we discuss how the recent advances in our understanding of chromatin biology may impact treatment of leukemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Methylation / genetics
  • DNA Methylation / immunology
  • Disease Progression
  • Epigenesis, Genetic / genetics*
  • Epigenesis, Genetic / immunology*
  • Hematopoiesis / genetics
  • Hematopoiesis / immunology
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia / genetics*
  • Leukemia / immunology*
  • Leukemia / pathology
  • Mutation
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Polycomb-Group Proteins / genetics

Substances

  • KMT2A protein, human
  • Polycomb-Group Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase