Jun 8, 2015

New Hope for an Intractable Leukemia?

Faculty & Staff, Research
Professor Aaron Schimmer
By

Heidi Singer

U of T researchers have made an exciting discovery in the search for new ways to shut down Human Acute Myeloid Leukemia (AML), a particularly aggressive blood cancer.

Professor Aaron Schimmer

Professor Aaron Schimmer and his team found high levels of a type of enzyme called ClpP in AML patients. This particular kind of enzyme, called a protease, normally maintains proteins in their proper state and cleans out the ‘garbage’ in the cell’s energy production system, the mitochondria.

Schimmer used chemical probes to destroy ClpP in mice with AML. He found that reducing the levels of ClpP killed cancer cells, but not normal ones.

The results were published June 8 in the journal Cancer Cell.

“We have a new potential target by which we may be able to treat a subset of AML patients,” says Schimmer, a Professor in the departments of medicine and medical biophysics, as well as the Institute of Medical Sciences. “Unfortunately, AML has a poor prognosis because there aren’t effective ways to treat it. We must find new therapies for this disease.”

Targeting the cell’s ‘garbage disposal system’ has already proven effective in other cancers. But this was the first time researchers looked at the function of the mitochondrial proteasome and the mitochondrial garbage disposal system says Schimmer, who is also a Staff Physician and Senior Scientist at the Princess Margaret Cancer Centre.

AML is particularly dependent on mitochondrial energy, prompting Schimmer to look into this part of the AML cell. A genetic screen identified ClpP as a critical part of the mitochondria and a target whose inhibition could kill AML cells.

The end goal of Schimmer’s discovery is to develop a drug that blocks ClpP and could one day be used to wipe out AML cells.

Schimmer’s findings shed light on the biology of the mitochondria in general – potentially opening up new areas of research into other forms of cancer and diseases.

“There’s a lot of interest now in targeting mitochondria and mitochondrial pathways in cancer and other disease,” he says. This system could be a major key to understanding and ultimately treating disease.”