Acute myeloid leukemia: New treatment overcomes chemo resistance
Scientists have revealed a new way to overcome chemotherapy resistance in acute myeloid leukemia. If the breakthrough in the laboratory is translated to the clinic, it could vastly improve the survival prospects for people with the rare blood cancer.
Investigators from the Ottawa Hospital and the University of Ottawa, both in Canada, saw that lack of a protein called MTF2 helps alter gene expression in acute myeloid leukemia (AML) cells in such a way that they will develop resistance to chemotherapy.
MTF2-deficient AML cells, the scientists found, overexpress a cancer-promoting gene called MDM2. It blocks the tumor-suppressor protein p53 and disrupts the cell-cycle process that leads to cell death when chemotherapy damages cells.
They then tested the effect of blocking MDM2 in a mouse model of chemoresistant AML. All the mice that received the treatment alongside chemotherapy survived and showed "complete remission," while those that only received chemotherapy died.
A report on the study — together with a detailed account of the underlying gene expression mechanisms involved — now features in the journal Cancer Discovery.
Co-senior study author William Stanford, who is a professor at the University of Ottawa and also works as a senior scientist at the Ottawa Hospital, says that the team was "blown away" by the results.
"If these findings," he continues, "hold up in clinical trials, we could have a new treatment for people who would almost certainly die of their disease today."
AML and chemoresistance
AML is a blood cancer that starts in bone marrow, which is where the body makes new blood cells. The cancer soon spreads into the bloodstream. In some cases, it can also spread to other parts of the body, such as the liver, spleen, lymph system, testicles, brain, and spinal cord.
Though rare, AML is the most common blood cancer in adults. It usually strikes after the age of 45, but it can also affect younger people, including children. The average risk of developing AML during one's lifetime in the United States is about 0.5 percent.
According to the American Cancer Society (ACS), there will be around 19,520 new cases of AML in the U.S. in 2018 and about 10,670 deaths to the disease.
Overcoming resistance to chemotherapy is a major challenge in treating AML. Most people who die of the disease succumb because of chemoresistance. Around one third of people do not respond at all, while 40–50 percent might respond at first, but then their cancer returns.
In previous work, Prof. Stanford and his team had discovered that MTF2 was important for making blood. They set up this new investigation to explore the protein's role in cancer.
