Researcher pieces together AML prognosis puzzle

October 15, 2012

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.

Explore further: Study reveals need for personalized approach in treatment of AML

Related Stories

Study reveals need for personalized approach in treatment of AML

May 16, 2011
A new discovery in mice by researchers at Wake Forest Baptist Medical Center may one day allow doctors to spare some patients with acute myeloid leukemia (AML) from toxic treatments, while also opening the door for new therapeutic ...

Gene discovery could improve treatment for acute myeloid leukemia

August 13, 2012
Scientists at Albert Einstein College of Medicine of Yeshiva University have made a discovery involving mice and humans that could mean that people with acute myeloid leukemia (AML), a rare and usually fatal cancer, are a ...

Two-faced leukemia?

December 12, 2011
One kind of leukemia sometimes masquerades as another, according to a study published online this week in the Journal of Experimental Medicine.

Cell death researchers identify new Achilles heel in acute myeloid leukemia

January 17, 2012
Melbourne researchers have discovered that acute myeloid leukaemia (AML), an aggressive blood cancer with poor prognosis, may be susceptible to medications that target a protein called Mcl-1.

Study pinpoints and plugs mechanism of AML cancer cell escape

January 18, 2012
A study published this week in the journal Leukemia identifies a mechanism that acute myeloid leukemia (AML) cells use to evade chemotherapy – and details how to close this escape route.

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 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.