Memorial Sloan-Kettering Cancer Center investigators have uncovered new clues about what controls the number of hematopoietic (blood-forming) stem cells (HSCs) and how these cells form the various types of mature circulating blood cells. The research was led by physician-scientist Stephen D. Nimer and published as the cover article of Cancer Cell in March. [PubMed Abstract]
The researchers studied mice they had engineered to lack a protein called MEF, which they discovered in the mid-1990s. MEF is a transcription factor (TF). TFs control when genes are turned on or off; MEF is an activator of gene expression. The investigators found that an absence of MEF induces a state of quiescence in HSCs. Because of this increased quiescence, or dormancy, mice lacking MEF were more resistant to the bone-marrow-suppressing effects of radiation and chemotherapy, surviving these treatments better than normal mice. The researchers also showed that reducing MEF levels in normal human HSCs similarly increased quiescence.
Based on these findings, the researchers suggest that treatments to diminish MEF may enhance recovery from cancer treatments because quiescent stem cells could repopulate depleted cells more quickly. But it is also possible that lowered MEF levels could protect leukemic stem cells by making them resistant to the same radiation and chemotherapy treatments. "Thus," Dr. Nimer said, "the hope is that our study will lead to better strategies for maintaining normal cells in a state of dormancy while we stimulate cancer cells to leave quiescence and therefore become more vulnerable to therapy."
