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:5/31/2016)... ... May 31, 2016 , ... CallTrackingMetrics's software gives ... monitor the performance of sales and support staff, and to efficiently route calls ... allows customers to record, transcribe, route, document, and report on everything going on ...
(Date:5/31/2016)... ... ... The Global Wellness Summit (GWS), an annual conference for international leaders ... spa and beauty in Europe. The organization asked its partner experts in Europe - ... - to forecast where wellness is headed in Europe. Predictions range from European nations ...
(Date:5/31/2016)... ... 2016 , ... Interest is on the rise for using the CRISPR-Cas9 system ... for RNAi hit validation. A key reason may be that high-throughput synthesis—combined with a ... RNA (crRNA) collections in arrayed formats. , Arrayed crRNA screens have ...
(Date:5/31/2016)... ... ... Dr. Charles A. Ditta attained his Doctor of Medical Dentistry Degree from ... where he graduated in the top ten percentile of his class. Dr. Ditta has ... has been a member in good standing for thirty years in the American Dental ...
(Date:5/30/2016)... (PRWEB) , ... May 30, 2016 , ... As the ... for their children and their efforts to keep their households lice free. , ... Hawaii are enacting new policies that keep kids in the classroom despite the fact ...
Breaking Medicine News(10 mins):
(Date:5/31/2016)... May 31, 2016  Diplomat Pharmacy, Inc. (NYSE: ... that Phil Hagerman , Chairman & CEO, and ... Blair 36 th Annual Growth Stock Conference in ... Mr. Whelan are scheduled to present at the conference on ... live audio-only webcast of the presentation and related presentation materials ...
(Date:5/31/2016)... , May 31, 2016 ... and Annotate Content From Elsevier,s ScienceDirect Database ... scientific, technical and medical information products and services, ... Berlin -based scientific collaboration platform PaperHive to enable ... over 12 million articles on ScienceDirect , ...
(Date:5/31/2016)... PUNE, India , May 31, 2016 ... 2016" market research report with comparative analysis of Asthma ... mechanism of action (MoA), route of administration (RoA) and ... and press releases. It also reviews key players involved ... on late-stage and discontinued projects. Complete report ...
Breaking Medicine Technology: