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 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.
Journal reference: PLoS ONE
Provided by Wake Forest University Baptist Medical Center
- Study reveals need for personalized approach in treatment of AML May 16, 2011 | not rated yet | 0
- Gene discovery could improve treatment for acute myeloid leukemia Aug 13, 2012 | not rated yet | 0
- Two-faced leukemia? Dec 12, 2011 | not rated yet | 0
- Protein that predicts prognosis of leukemia patients may also be a therapeutic target Jul 08, 2010 | not rated yet | 0
- Cell death researchers identify new Achilles heel in acute myeloid leukemia Jan 17, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Cancer 1 hour ago | not rated yet | 0 |
A new study conducted using extensive medical records of over one million Israeli adolescents before military service shows clearly how exposure to the Israeli sun of young, light-skinned children increases substantially ...
Cancer 3 hours ago | not rated yet | 0
A new measure of the heterogeneity – the variety of genetic mutations – of cells within a tumor appears to predict treatment outcomes of patients with the most common type of head and neck cancer. In the May 20 issue ...
Cancer 7 hours ago | not rated yet | 0
Researchers at Mayo Clinic have developed a promising method to distinguish between pancreatic cancer and chronic pancreatitis—two disorders that are difficult to tell apart. A molecular marker obtained from pancreatic ...
Cancer 7 hours ago | not rated yet | 0
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer May 19, 2013 | not rated yet | 0
1 hour ago | not rated yet | 0 |
There is a link between use of anabolic-androgenic steroids and reduced mental health later in life. This is the main conclusion of a new study on elite male strength athletes that researchers from the University of Gothenburg ...
21 minutes ago | not rated yet | 0
High-intensity, short duration warm up activities at half time intervals boost athletic performance, a study of soccer players has found.
33 minutes ago | not rated yet | 0
(Medical Xpress)—Bullying because of perceived sexual orientation is prevalent among school-aged youths, according to a study led by Donald Patrick, professor of health services at the UW School of Public ...
53 minutes ago | not rated yet | 0
Patients suffering from chronic obstructive pulmonary disease (COPD) typically suffer from depression more frequently than those without COPD, resulting in higher levels of disability and illness and increasing the overall ...
1 hour ago | not rated yet | 0