Title:The Role of DNA Repair Pathways in AML Chemosensitivity
Volume: 19
Issue: 10
Author(s): Elizabeth A. Pearsall, Lisa F. Lincz and Kathryn A. Skelding*
Affiliation:
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, New South Wales,Australia
Keywords:
Acute myeloid leukaemia, base excision repair, chemosensitivity, direct enzymatic repair, DNA repair, homologous
recombination, nucleotide excision repair, non-homologous end joining.
Abstract: Background: Defects in DNA repair pathways are causal factors for a plethora of solid tumours,
but are only just beginning to be explored in haematological malignancies. Genomic instability,
including mutations in DNA sequences, chromosomal aneuploidy, translocations and gene amplifications
contribute to the development and progression of AML. Prior DNA damaging agent exposure
enhances the risk of developing AML, as does inheritance of genetic syndromes that involve alterations
in DNA repair pathways. Furthermore, these same variations are associated with sensitivity
and resistance to a range of chemotherapeutics. Taken together, these studies suggest that defects
within DNA repair pathways are involved in the pathogenesis and prognosis of AML.
Objective: This review summarises the major DNA repair pathways, and presents an overview of current
data on DNA damage repair abnormalities in AML as they pertain to the development of resistance
and sensitivity to chemotherapeutics in AML. Additionally, the use of drugs that modulate these
pathways as new treatments for AML will be explored herein.
Conclusion: This review highlights that abnormalities in DNA repair mechanisms in AML cells are
potential novel treatment targets for AML patients with disease that is resistant to current therapies.
