Featured Research

from universities, journals, and other organizations

Researcher pieces together AML prognosis puzzle

Date:
October 15, 2012
Source:
Wake Forest Baptist Medical Center
Summary:
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 researcher decided to take a closer look.

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 white blood cells that usually protect people from infections become cancerous, leading to bone marrow failure 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 PLOS ONE.

To test the hypothesis, Pardee set out to make leukemia cells 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 mouse model 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 retrovirus and put it into two separate human cell lines acquired from AML patients.

"We looked to see if the cells in both models were resistant to chemotherapy. The answer is 'yes,' though the resistance in mouse cells 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.

Funding for the research was obtained from The Doug Coley Leukemia Research Foundation, The MacKay Foundation for Cancer Research, The Leight Endowed Research Fund, and the Frances P. Tutwiler Fund. Additional support provided by grant P30CA012197 from the National Cancer Institute.


Story Source:

The above story is based on materials provided by Wake Forest Baptist Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Timothy S. Pardee. Overexpression of MN1 Confers Resistance to Chemotherapy, Accelerates Leukemia Onset, and Suppresses p53 and Bim Induction. PLoS ONE, 2012; 7 (8): e43185 DOI: 10.1371/journal.pone.0043185

Cite This Page:

Wake Forest Baptist Medical Center. "Researcher pieces together AML prognosis puzzle." ScienceDaily. ScienceDaily, 15 October 2012. <www.sciencedaily.com/releases/2012/10/121015151157.htm>.
Wake Forest Baptist Medical Center. (2012, October 15). Researcher pieces together AML prognosis puzzle. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2012/10/121015151157.htm
Wake Forest Baptist Medical Center. "Researcher pieces together AML prognosis puzzle." ScienceDaily. www.sciencedaily.com/releases/2012/10/121015151157.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins