Researcher pieces together AML prognosis puzzle

When patients suffering from Acute Myeloid Leukemia (AML) express high levels of the gene, MN1, an already aggressive leukemia is accelerated and shortens survival time. While that's a known fact, the mechanisms involved aren't well understood which is why a Wake Forest Baptist Medical Center researcher decided to take a closer look.

Timothy S. Pardee, M.D., Ph.D., an assistant professor of hematology and oncology at Wake Forest Baptist, said that previous studies of AML have shown that when patients express high levels of the MN1 gene, chemotherapy doesn't help as much and they die sooner from the disease.

"No one really knows why this is happening," Pardee said. "Because this disease is treated only with chemotherapy we hypothesized that high expression of this gene, would make the leukemia resistant to chemotherapy treatment."

AML is an aggressive malignancy of the bone marrow where the that usually protect people from infections become cancerous, leading to and death. This cancer is characterized by a high relapse rate and resistance to chemotherapy. In older patients the average survival for those with high MN1 expression is less than six months while for low expressers it is closer to nine months.

The research was published online in August in .

To test the hypothesis, Pardee set out to make express the MN1 gene and looked at how they changed in response to chemotherapy. He did this by using a retrovirus to add the MN1 gene and force high levels of expression in a genetically-defined of AML. This resulted in the mice having a worse prognosis compared to the group of mice that didn't get the MN1 gene. In addition, he also took the same and put it into two separate human cell lines acquired from .

"We looked to see if the cells in both models were resistant to chemotherapy. The answer is 'yes,' though the resistance in was more evident," Pardee said.

Then Pardee compared mouse leukemia cells that expressed high levels of MN1 and those that didn't to investigate what occurs when the cells are hit with chemotherapy. "It turns out there is a key protein, p53, that tells the cancer cells when DNA damage is too much and that it's time to commit suicide," Pardee said. "But p53 was not being made to the same level in those cells that were making the MN1 gene and the ability to turn that DNA damaged signal into leukemia cell death was much lower in the cells that make MN1 protein."

Pardee said he looked at some other proteins involved in leukemia cell death and found that an additional protein called BIM – which promotes cell death – was also being shut down in the cells that made higher levels of MN1.

"We know it's happening, but we don't know how. Our ultimate goal is to figure out better ways to treat these patients that do so poorly," Pardee said. "We were able to make the leukemia cells a little bit more sensitive to chemotherapy when we treated them with a drug that increases p53 levels, suggesting it might be a strategy to look at for patients who have this high MN1 expression.

Related Stories

Two-faced leukemia?

date Dec 12, 2011

One kind of leukemia sometimes masquerades as another, according to a study published online this week in the Journal of Experimental Medicine.

Recommended for you

DNA blood test detects lung cancer mutations

date 11 hours ago

Cancer DNA circulating in the bloodstream of lung cancer patients can provide doctors with vital mutation information that can help optimise treatment when tumour tissue is not available, an international group of researchers ...

Tumors prefer the easy way out

date 13 hours ago

Tumor cells become lethal when they spread. Blocking this process can be a powerful way to stop cancer. Historically, scientists thought that tumor cells migrated by brute force, actively pushing through whatever ...

Brain tumors may be new targets of Ebola-like virus

date 13 hours ago

Brain tumors are notoriously difficult for most drugs to reach, but Yale researchers have found a promising but unlikely new ally against brain cancers—portions of a deadly virus similar to Ebola.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.