Arsenic triggers unique mechanism in rare leukemia

Dartmouth Medical School (DMS) researchers have identified a new way that arsenite, a form of arsenic, acts in treating a rare cancer known as APL, or acute promyelocytic leukemia.

"We knew that arsenite was particularly effective against this cancer, and we wanted to figure out why," says Sutisak Kitareewan, an author on this paper and an instructor of pharmacology and toxicology at DMS. "Now we know that arsenite destabilizes lysosomes, a part of a cell that contains certain enzymes, which, when released, often kill APL cells."

APL is caused by the swapping of chromosomes 15 and 17, which forms a fusion protein. This fusion protein prevents certain blood cells from maturing and leads to an accumulation of immature leukemia cells. Researchers found that arsenite causes rapid destabilization of the lysosome in cells, and that breaks the lysosome apart, releasing enzymes that destroy these particular kinds of leukemia cells.

"We hope this finding will be used to inform further research into treating APL," says co-author Ethan Dmitrovsky, professor of medicine and of pharmacology and toxicology, who is also affiliated with the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center. "We also hope that further studies examine if this same mode of action is the basis for arsenic toxicity."

In addition to Kitareewan and Dmitrovsky, the other authors on the paper include B.D. Roebuck, professor of pharmacology and toxicology; Eugene Demidenko, research professor of community and family medicine in the area of biostatistics; and Roger Sloboda, the Ira Allen Eastman Professor of Biological Sciences. Dmitrovsky also holds the Andrew G. Wallace Professorship at Dartmouth.

This research was supported by funds from the National Institutes of Health and the National Science Foundation. - Dartmouth College