The DNA Damage Response, DNA Repair, and AML

  • David P. Steensma
Chapter
Part of the Contemporary Hematology book series (CH)

Abstract

Acute myeloid leukemia (AML)—especially when the condition arises out of a pre-existing melodysplastic syndrome or follows prior therapy with alkylating agents or ionizing radiation—is frequently associated with complex bone marrow karyotypes, including multiple numeric chromosomal abnormalities, diminutive marker chromosomes of uncertain derivation, and interstitial gains and losses of genetic material. In addition, a variety of inheritied syndromes with DNA repair defects convey a high risk of myelodysplasia and leukemia. Together, these pieces of evidence suggest that a fundamental defect in the DNA damage recognition and response pathways is an important component of leukemogenesis. Here, the basic DNA damage recognition and repair pathways are reviewed and data on known DNA repair abnormalities in acute leukemia and myelodysplastic syndrome are summarized. In addition, inherited syndromes with a DNA repair defect that predisposes to leukemia are outlined, including Fanconi anemia, Bloom syndrome, ataxia-telangiectasia and ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome, Seckel syndrome, and others.

Key Words

DNA repair DNA damage recognition base excision repair nucleotide excision repair homologous recombination nonhomologous end joining Fanconi anemia Bloom syndrome RecQ helicases inherited syndromes ataxia-telangiectasia Nijmegen breakage syndrom Seckel syndrome nibrin 
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Copyright information

© Humana Press Inc., Totowa, NJ 2007

Authors and Affiliations

  • David P. Steensma
    • 1
  1. 1.Division of HematologyMayo ClinicRochester

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