Quiescent blood stem cells may be linked to genetic mutations that can lead to leukemia, according to a study published in Cell Stem Cell (2010 Aug 6;7(2):174-85).
Researchers from the University of California San Francisco (UCSF) conducted a study to determine if blood stem cells in the quiescent state were at greater risk for incurring genetic mutation in the process of repairing damaged DNA.
From the study, researchers were able to determine that both quiescent and proliferating blood stem cells have protective mechanisms that ensure their survival in response to exposure to ionizing irradiation, as occurs from sources such as the sun and X-rays. However, they discovered that quiescent and proliferating blood stem cells have unique DNA repair mechanisms. The authors explained that while the repair mechanism used by the quiescent cells is defective, it is not detrimental for the body in evolutionary terms.
“Our results demonstrate that quiescence is a double-edged sword, protecting hematopoetic stem cells from cellular stress but rendering them intrinsically vulnerable to mutagenesis following DNA damage,” said senior author Emmanuelle Passegué, PhD, associate professor of medicine and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.
The authors said that the findings suggest a strategy for reducing the risk of leukemia resulting from chemotherapy used to treat solid tumors. “Existing drugs, such as G-CSF and prostaglandins, could be used to induce hematopoetic stem cells to proliferate prior to the use of therapy with DNA damaging agents,” said Mary Mohrin, a graduate student in the Passegué lab. “This could enhance DNA repair fidelity and reduce the risk of leukemia development.”