Recent studies have implicated reduced levels of a transcription factor called MEF with subtypes of leukemia. Drs. Stephen D. Nimer and Daniel Lacorazza from Memorial Sloan-Kettering Cancer Center and colleagues examined the blood cells of mice that do not express MEF in their bone marrow and found an increased population of hematopoietic (blood-forming) stem cells (HSCs). HSCs are immature cells in the bone marrow that have the capacity to differentiate into all types of mature blood cells. A delicate balance exists between self-renewal and differentiation of HSCs because the body must retain a sufficient population of HSCs while continually producing the multitude of new blood cells that are needed each day.
The researchers demonstrated that MEF regulates a little-understood state of quiescence that enables HSCs to exist in a kind of suspended animation until they are recruited to promote rapid repopulation of depleted blood cells, as would be needed following treatment with chemotherapy or radiation therapy. MEF-deficient mice accumulated quiescent HSCs with the capacity for repopulation and demonstrated enhanced resistance to the effects of chemotherapeutic drugs and radiation, which is also seen in wild-type mice transplanted with MEF-deficient HSCs. "This feature can also be helpful to maintain HSCs in an undifferentiated state during gene therapy protocols," explains Dr. Lacorazza, now a faculty member at Baylor College of Medicine.
These results suggest that MEF regulates HSCs' decision to re
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Contact: Heidi Hardman
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Cell Press
13-Mar-2006