Navigation Links
Inhibitors of shuttle molecule show promise in acute leukemia
Date:6/19/2012

  • An estimated 10,200 Americans will die of acute myeloid leukemia (AML) in 2012, so new ways of treating the disease are needed.
  • This study uses a novel class of experimental drugs to halt a process that helps AML cells develop and survive.
  • The findings show that the agent is promising and should be considered for clinical trials testing.

COLUMBUS, Ohio 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.

'/>"/>
Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related medicine news :

1. Molecule movements that make us think
2. Prions in the brain eliminated by homing molecules
3. Researchers identify a life-and-death molecule on chronic leukemia cells
4. Early Study Finds Some Promise for Lung Cancer Vaccine
5. Novel compound demonstrates anti-leukemic effect in zebrafish, shows promise for human treatment
6. Nonsurgical Method to Measure Brain Pressure Shows Promise
7. Immunotherapy for elderly cancer patients finds new promise in drug combination
8. Experimental Pill for Multiple Sclerosis Shows Promise
9. Mechanical tissue resuscitation technology shows promise
10. Brain Tumor Vaccine Shows Promise in Early Trial
11. New Method to Reveal Alzheimers Marker Shows Promise
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX ... Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s package transforms over ... Cut Pro X . Simply select a ProHand generator and drag it above media ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the benefits of moderation, ... the latter, setting the bar too high can result in disappointment, perhaps even self-loathing. ... toward their goal. , Research from PsychTests.com reveals that behind the ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension Association ... it will receive two significant new grants to support its work to advance ... 25th anniversary by recognizing patients, medical professionals and scientists for their work in ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. are sharpening their pencils ... an essay contest in which patients and their families pay tribute to a genetic ... 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. ...
(Date:6/24/2016)... , ... June 24, 2016 , ... National recruitment firm ... life sciences executive with extensive sequencing and genomics experience, as Vice President of North ... Ms. Hill will be responsible for leading the sales team in the commercialization of ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 Dehaier Medical Systems ... "Company"), which develops, markets and sells medical devices and ... , signed a strategic cooperation agreement with Hongyuan Supply ... Supply Chain") on June 20, 2016, to develop Dehaier,s ... strategic cooperation agreement, Dehaier will leverage Hongyuan Supply Chain,s ...
(Date:6/24/2016)... , June 24, 2016   Pulmatrix, Inc ., ... developing innovative inhaled drugs, announced today that it was ... Investments reconstituted its comprehensive set of U.S. and ... "This is an important milestone for Pulmatrix," said Chief ... shareholder awareness of our progress in developing drugs for ...
(Date:6/23/2016)... Research and Markets has announced the addition of ... report to their offering. ... kidney failure, it replaces the function of kidneys by removing ... thus the treatment helps to keep the patient body,s electrolytes ... Increasing number of ESRD patients & substantial healthcare expenditure ...
Breaking Medicine Technology: