The Very, Very Bad Guys
Though we usually view stem cells as effective therapeutics, some are deadly. Tomasz Skorski, professor of microbiology and immunology, studies how to stop one particularly insidious group of leukemia stem cells.
“This is a subpopulation of leukemia cells that can´t be eradicated with any known drugs,” says Skorski, also an associate professor in the Fels Institute for Cancer Research and Molecular Biology at Temple. “They are the very, very bad guys.”
Existing drugs can treat the majority of leukemia cells, but the disease´s stem cells have a genetic instability that contributes to their resistance. That subpopulation can cause genetic aberrations that can become immune to treatments. They then continue to mutate and reproduce. The body can harbor several million ultra-resistant leukemic stem cells that then deploy throughout the body and take over quickly.
Skorski and his team focus on the mutations. A clue could lie in the cells´ levels of reactive oxygen species, which cause tiny tears in our DNA. (Leukemia stem cells accumulate a lot of them.)
Whether leukemic or healthy, DNA tears have to be repaired in all cells. However, a mechanism not present in normal cells enables leukemia stem cells to repair faster and more efficiently than healthy cells. Skorski aims to target those repair mechanisms, so the breaks will accumulate and cause the cells to die off.
“We propose that we don´t have to use any toxic drugs [for treatment],” Skorski says. “If you target the pathways, then the leukemia cells can´t repair. At the same time, normal cells use different pathways, so they´ll be fine.”
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