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.