Leukemia :: Arsenic triggers unique mechanism in rare leukemia

Dartmouth Medical School 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. Their study is published in the Jan_3 issue of the Journal of the National Cancer Institute.

“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.”


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Leukemia :: Arsenic triggers unique mechanism in rare leukemia

There are few treatments for a rare cancer called acute promyelocytic leukemia (APL). Arsenite is a form of arsenic that’s particularly effective against this cancer. In a new study, researchers identify a novel mechanism by which arsenite acts in APL cells.

APL is caused by a translocation of chromosomes 15 and 17 that forms a fusion protein between two genes called promyelocytic leukemia protein (PML) and retinoic acid receptor alpha (RAR-alpha). This fusion protein prevents certain blood cells from maturing and leads to an accumulation of these immature leukemia cells. In the new study, Sutisak Kitareewan, Ph.D., of Dartmouth Medical School, and colleagues find that arsenite destabilizes lysosomes in APL cells. Lysosomes contain enzymes that can break down various cellular components. Destabilized lysosomes release enzymes that degrade the faulty PML/RAR-alpha protein, a step that often leads to the death of the cancerous APL cells.


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