Navigation Links
Singapore research team identifies new drug target in deadly form of leukemia
Date:6/3/2013

SINGAPORE A research team led by the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has identified ways to inhibit the function of a key protein linked to stem cell-like behavior in terminal-stage chronic myeloid leukemia (CML), making it possible to develop drugs that may extend the survival of these patients.

The study, published in the prestigious international journal Proceedings of the National Academy of Sciences, is the result of a long-standing collaboration between Duke-NUS, the Experimental Therapeutics Centre at the Agency for Science, Technology and Research (A*STAR), and the Singapore General Hospital that is focused on developing effective therapies in CML.

CML is a blood cancer that has seen tremendous improvement in treatment outcomes following the introduction of tyrosine kinase inhibitor (TKI) drugs that specifically target the BCR-ABL fusion gene, a genetic abnormality that is characteristic of CML. However, when CML progresses to its terminal stage, known as the blast crisis phase, TKI drugs become ineffective and patients with blast crisis CML rapidly succumb to the disease.

"TKI therapy is highly effective in chronic phase CML, and enables most patients to survive many years. In contrast, patients with blast crisis CML usually succumb to their disease within one year, with most patients dying because they develop drug resistance to TKI therapy," said principal investigator Ong Sin Tiong, associate professor and head of the Laboratory of Hematologic Malignancies in the Cancer and Stem Cell Biology Program at Duke-NUS.

A subset of cells associated with blast crisis CML exhibit characteristics of self-renewing stem cells, suggesting that targeting this particularly malignant and drug-resistant population would be effective in treating blast crisis CML. The team therefore searched for novel targets that will specifically eliminate these cancer stem cells.

Through their efforts, the team identified a protein enzyme, known as the MNK kinase, that was abnormally activated in clinical samples taken from patients with blast crisis CML. Experiments conducted in the lab further unraveled how MNK kinase activation plays a critical role in the progression of CML to the blast crisis phase, and confers stem cell-like behavior on blast crisis cells.

The team tested a panel of drugs that inhibit MNK kinase activity and found that these MNK inhibitors were effective in preventing blast crisis cells from behaving like cancer stem cells in both in vitro laboratory tests and animal studies.

"Our studies identify the MNK kinases as an important therapeutic target in blast crisis CML, and suggest that drug inhibition of MNK kinase will be useful in overcoming TKI resistance, and improving the survival of patients with blast crisis CML," said Ong, who is also a visiting consultant at the National Cancer Center Singapore and Singapore General Hospital.

Importantly, the MNK inhibitor drugs do not appear to be toxic to normal blood stem cells, indicating that drugs targeting MNK kinases may not cause harmful side effects. Ong said he hopes the findings from this study will open new research directions in the treatment of blast crisis CML.

"We are currently collaborating with the Experimental Therapeutics Centre and Singapore General Hospital to develop new drugs to simultaneously target the MNK and the BCR-ABL kinases. The development of dual MNK and BCR-ABL kinase inhibitors to treat patients with blast crisis CML may enhance the survival of patients with this deadly disease," Ong said. He added he ho estimates it will take a few years before these drugs can enter into clinical trials for blast crisis CML.


'/>"/>

Contact: Juliana Chan
editor@asianscientist.com
65-829-93719
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. First in the world - Singapore scientists discover genes responsible for cornea blindness
2. National Heart Centre Singapore develops worlds first human heart cell model
3. Singapore scientists find genes associated with glaucoma, a major cause of eye blindness
4. NUS launches new book on Singapores rainforests and new free digital nature archive
5. Made-in-Singapore H5N1 diagnostic kit -- detects all known strains of H5N1 virus with a single test
6. Researchers develop a faster method to identify Salmonella strains
7. Researchers document acceleration of ocean denitrification during deglaciation
8. Researchers design sensitive new microphone modeled on fly ear
9. Researchers help threatened wheat crops in Asia, Africa
10. Roy J. Carver Charitable Trust funds new research focus at Institute for Genomic Biology
11. U of A medical researchers ID genetic marker for sporadic breast cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... DUBLIN , Mar 24, 2017 Research ... Vehicle Access System Market Analysis & Trends - Industry Forecast to ... ... poised to grow at a CAGR of around 15.1% over the ... This industry report analyzes the market estimates and forecasts for ...
(Date:3/22/2017)... 21, 2017   Neurotechnology , a provider ... today announced the release of the SentiVeillance ... improved facial recognition using up to 10 surveillance, ... computer. The new version uses deep neural-network-based facial ... it utilizes a Graphing Processing Unit (GPU) for ...
(Date:3/20/2017)... March 20, 2017 At this year,s CeBIT Chancellor ... biometrics manufacturer DERMALOG. The Chancellor came to the DERMALOG stand together with ... this year,s CeBIT partner country. At the largest German biometrics company the ... fingerprint, face and iris recognition as well as DERMALOGĀ“s multi-biometrics system.   ... ...
Breaking Biology News(10 mins):
(Date:7/26/2017)... ... July 25, 2017 , ... ... to announce that its regenerative stem cell therapy has been used on more ... successful treatment for horses with potentially fatal injuries to tendons and ligaments. , ...
(Date:7/26/2017)... FL (PRWEB) , ... July 26, 2017 , ... ... learning algorithms targeted towards leveraging the years of diagnostic excellence by Mayo Clinic ... The first product suite will be distributed through the Microsoft Azure platform ...
(Date:7/25/2017)... (PRWEB) , ... July 25, 2017 , ... Fiberstar, ... food and beverage industry, offers Citri-Fi® 125. This natural citrus fiber is used to ... and extend real tomato in sauces, condiments and spreads. Today, more than ever, consumers ...
(Date:7/24/2017)... 2017 Intralytix, Inc. announced that it received ... French family group. This investment marks the beginning of ... commercialize bacteriophage-based products, for various benefits in human health ... As a global key ... markets innovative solutions for baking, food taste & pleasure, ...
Breaking Biology Technology: