Format

Send to

Choose Destination
See comment in PubMed Commons below
Leuk Res. 2014 Jan;38(1):95-102. doi: 10.1016/j.leukres.2013.07.008. Epub 2013 Aug 16.

Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome.

Author information

1
Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
2
Department of Radiation Oncology and Marlene & Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA. Electronic address: aplanp@mail.nih.gov.

Abstract

The myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it has been suggested that additional mutations lead to progression of MDS to AML, the causative agent(s) for such mutations remains unclear. Oxidative stress is a potential cause, therefore, we evaluated levels of reactive oxygen species (ROS) in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for MDS. Increased levels of ROS were detected in bone marrow nucleated cells (BMNC) that express CD71, a marker for cell proliferation, as well as immature, lineage negative bone marrow nucleated cells from NHD13 mice. In addition to the increase in ROS, increased DNA double strand breaks and activation of a G2/M phase cell cycle checkpoint were noted in NHD13 BMNC. Finally, using an in vivo assay for mutation frequency, we detected an increased mutation frequency in NHD13 BMNC. These results suggest that oxidative stress may contribute to disease progression of MDS to AML through ineffective repair of DNA damage and acquisition of oncogenic mutations.

KEYWORDS:

AML; Big Blue(®) mice; MDS; Mutation; NHD13; ROS

PMID:
23958061
PMCID:
PMC3872269
DOI:
10.1016/j.leukres.2013.07.008
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center