Inhibitors of shuttle molecule show promise in acute leukemia
A novel family of experimental agents that blocks a molecule from shuttling proteins out of the cell nucleus might offer a new treatment for people with acute leukemia, according to a study by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
The agents, called KPT-SINEs (selective inhibitors of nuclear export), target a transport protein called CRM1. Using acute myeloid leukemia (AML) cells and an animal model, the researchers showed that these agents inhibited leukemia-cell proliferation, arrested cell division, and induced cell death and differentiation.
In the animal model of AML, KPT-SINEs described by the researchers as one of the most advanced agents in pre-clinical development extended survival by 46 percent compared with controls.
KPT-SINEs were particularly effective when the leukemia cells also had mutations in the tumor-suppressor gene NPM1, which are present in about one-third of all adult AML.
The findings were published online in the journal Blood.
"Our study suggests that these agents might be an effective therapy for AML, particularly for patients with NPM1 mutations," says principal investigator Dr. Ramiro Garzon, assistant professor of medicine and a researcher with the OSUCCC James Molecular Biology and Cancer Genetics Program.
"We hope to start a phase I trial using one of these agents soon and to pursue further preclinical studies using this drug in combination with other current chemotherapies," Garzon says.
CRM1 normally transports molecules out of the cell nucleus to the surrounding cytoplasm. In acute leukemia cells, the molecule carries tumor-suppressor, apoptotic and other protective proteins out of the nucleus, thereby contributing to leukemia development. Karyopharm Therapeutics, Inc., developed KPT-SINEs. This study also showed that these agents:
- Reduce the amount of CRM1 protein in the nucleus and increase the amount of tumor-suppressor protein such as p53 and NPM1 in AML cells.
- Strongly down-regulate FLT3 and KIT, oncogenes that are commonly overexpressed in AML.
- Increase survival in a leukemia animal model, with treated mice living an average of 39 days versus 27 days for untreated animals.
Journal reference: Blood
Provided by Ohio State University Medical Center
- Novel export-inhibitor shows promise for treating chronic lymphocytic leukemia Dec 12, 2011 | not rated yet | 0
- Two-faced leukemia? Dec 12, 2011 | not rated yet | 0
- 'Vicious circle' offers new acute leukemia treatment target Apr 13, 2010 | not rated yet | 0
- A microRNA prognostic marker identified in acute leukemia May 14, 2012 | not rated yet | 0
- A miR boost enables acute leukemia cells to mature Apr 03, 2009 | 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
How can there be a term called "intestinal metaplasia" of stomach
23 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
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...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 11 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 12 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 13 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 14 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 16 hours ago | not rated yet | 0
Is it permissible to harm one to save many? Those who tend to say "yes" when faced with this classic dilemma are likely to be deficient in a specific kind of empathy, according to a report published in the scientific journal ...
1 hour ago | not rated yet | 0 |
Phthalates: Study links chemicals widely found in plastics, processed food to elevated blood pressure in children, teens
Plastic additives known as phthalates (pronounced THAL-ates) are odorless, colorless and just about everywhere: They turn up in flooring, plastic cups, beach balls, plastic wrap, intravenous tubing and—according to the ...
2 hours ago | not rated yet | 1 |
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
18 hours ago | 4.2 / 5 (5) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
16 hours ago | 4.9 / 5 (14) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
18 hours ago | 4.6 / 5 (7) | 0 |
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
13 hours ago | 5 / 5 (5) | 0 |