Dartmouth researchers identify why it works
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. Their
study is published in the Jan. 3 issue of the Journal of the National Cancer
Institute.
Dartmouth researchers have identified why arsenite is an effective treatment
against a rare form of leukemia. Seated: Sutisak Kitareewan. Standing (from
left) Ethan Dmitrovsky, Roger Sloboda, Eugene Demidenko, and B.D. Roebuck.
(Photo by Joseph Mehling '69)
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"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 will 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.
The research was supported by funds from the National Institutes of Health and the National Science Foundation.
By SUSAN KNAPP
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