DNA damage response and hematological malignancy

Int J Hematol. 2017 Sep;106(3):345-356. doi: 10.1007/s12185-017-2226-0. Epub 2017 Apr 3.

Abstract

DNA damage is a serious threat to cellular homeostasis. Damaged DNA leads to genomic instability, mutation, senescence, and/or cell death. DNA damage triggers a cellular response called the DNA damage response (DDR), followed by activation of the DNA repair machinery. DDR both maintains cellular homeostasis and prevents cancer development. Germ line mutation of DDR-associated genes can lead to cancer-susceptible syndromes. Somatic mutation of DDR-associated genes has also been reported in various tumors, including hematological malignancies. Therapeutic approaches that target the DDR and DNA repair are thus now being developed. Understanding the mechanism(s) underlying DDR and DNA repair will increase our knowledge of cancer etiology and facilitate development of cancer therapies.

Keywords: ATM; Caner susceptible syndrome; DNA damage response; DNA repair; Hematological malignancy.

Publication types

  • Review

MeSH terms

  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / physiology
  • Cell Cycle Checkpoints / genetics
  • DNA / genetics
  • DNA Damage / genetics*
  • DNA, Single-Stranded / genetics
  • Genomic Instability / genetics
  • Germ-Line Mutation / genetics
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy
  • Humans
  • Molecular Targeted Therapy

Substances

  • DNA, Single-Stranded
  • DNA
  • Ataxia Telangiectasia Mutated Proteins