PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Singapore research team identifies new drug target in deadly form of leukemia

2013-06-04
(Press-News.org) 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.

### Dr. Sharon Lim, a research fellow at Duke-NUS, is the first author of the study. Funding for the study was provided by the Duke–National University of Singapore Signature Research Program funded by A*STAR; the Ministry of Health (Singapore); and the National Research Foundation Singapore Clinician Scientist Award, awarded to Ong by the National Medical Research Council.


ELSE PRESS RELEASES FROM THIS DATE:

Thompson Ridge Fire, New Mexico

2013-06-04
NASA's Aqua satellite captured an image of a large light-brown colored plumes of smoke from two large fires burning in New Mexico: the Thompson Ridge Fire (left) and the Tres Lagunas Fire (right). Inciweb reported that the Thompson Ridge Fire is located in the Valles Caldera National Preserve, located about two miles northeast of La Cueva, New Mexico. The fire is reported to be human-caused, and started on May 31, 2013. So far, 1,906 acres have burned in the Preserve. The Tres Leguans Fire was started by a downed power line on May 30. The fire started about 10 miles ...

Discovery's Edge online issue

2013-06-04
Here are highlights from the online issue of Discovery's Edge, Mayo Clinic's research magazine. You may cite and link to this publication as often as you wish. Republication is allowed with proper attribution. Please include the following subscription information as your editorial policies permit: Visit Discovery's Edge for subscription information. Regenerating Heart Tissue Through Stem Cell Therapy Read the details of how Mayo Clinic's unique stem cell technique restored strength and endurance to heart attack patients in three European countries. This groundbreaking ...

Manipulating memory in the hippocampus

2013-06-04
In the brain, cell-to-cell communication is dependent on neurotransmitters, chemicals that aid the transfer of information between neurons. Several proteins have the ability to modify the production of these chemicals by either increasing or decreasing their amount, or promoting or preventing their secretion. One example is tomosyn, which hinders the secretion of neurotransmitters in abnormal amounts. Dr. Boaz Barak of Tel Aviv University's Sagol School of Neuroscience, in collaboration with Prof. Uri Ashery, used a method for modifying the levels of this protein in the ...

Powerhouse Fire, California

2013-06-04
NASA's Terra satellite captured this natural-color satellite image of California's Powerhouse Fire with the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument on June 1, 2013. Actively burning areas, detected by MODIS's thermal bands, are outlined in red. According to the CBSnews.com, "Nearly 3,000 people from some 700 homes were under evacuation orders Monday as a wildfire north of Los Angeles kept growing, feeding on old, dry brush, some of which hadn't burned in decades. The blaze had burned about 46 square miles in the mountains and canyons of the ...

Tres Lagunas Fire, New Mexico

2013-06-04
NASA's Aqua satellite captured an image of a large light-brown colored plume of smoke blowing east-southeast from the Tres Lagunas Fire burning in New Mexico. On June 3, the smoke is forecast to blow in a more northerly and easterly direction, affecting Las Vegas, I-25 and surrounding communities. The Moderate Resolution Imaging Spectroradiometer (MODIS) instrument aboard NASA's Aqua satellite has infrared capabilities that can detect heat from the various wildfires. This image was captured on May 31, 2013 21:00 UTC (5 p.m. EDT/3p.m. MT). In the MODIS images, fires, or ...

Women reject sexually promiscuous peers when making female friends

2013-06-04
ITHACA, N.Y. – College-aged women judge promiscuous female peers – defined by bedding 20 sexual partners by their early 20s – more negatively than more chaste women and view them as unsuitable for friendship, finds a study by Cornell University developmental psychologists. Notably, participants' preference for less sexually active women as friends remained even when they personally reported liberal attitudes about casual sex or a high number of lifetime lovers. Men's views, on the other hand, were less uniform – favoring the sexually permissive potential friend, the ...

June 2013 story tips

2013-06-04
TRANSPORTATION – Better, cleaner engines . . . Air in the United States could be cleaner in years to come because of a laboratory researchers expect will help in the development of new standards for fuel economy and emissions evaluations. The Vehicle Systems Integration Laboratory provides unprecedented capabilities that will be invaluable to manufacturers of diesel and conventional engines, transmissions, and other drivetrain and emissions components. The payoff is that manufacturers can test different designs under real-world conditions, saving time and money. "We can ...

NTRK1: A new oncogene and target in lung cancer

2013-06-04
To the list of oncogenic drivers of lung cancer that includes ALK, EGFR, ROS1 and RET, results of a University of Colorado Cancer Center study presented at ASCO 2013 show that mutations in the gene NTRK1 cause a subset of lung cancers. "We're reconceptualizing lung cancer as many, related diseases. And we need to learn to identify and treat each individually. We can treat the forms of the disease that depend on ALK and EGFR mutations. We're getting very close to treating lung cancers that depend on ROS1 and RET. And now we show another oncogenic driver of the disease ...

Are smartphones disrupting your sleep? Mayo Clinic study examines the question

2013-06-04
BALTIMORE -- Smartphones and tablets can make for sleep-disrupting bedfellows. One cause is believed to be the bright light-emitting diodes that allow the use of mobile devices in dimly lit rooms; the light exposure can interfere with melatonin, a hormone that helps control the natural sleep-wake cycle. But there may be a way to check your mobile device in bed and still get a good night's sleep. A Mayo Clinic study suggests dimming the smartphone or tablet brightness settings and holding the device at least 14 inches from your face while using it will reduce its potential ...

Butterfly on the brink: First Schaus female found in a year raises hope for revival of species

2013-06-04
GAINESVILLE, Fla. — The fate of a species may rest upon a single butterfly captured in late May by University of Florida lepidopterists. A UF research technician netted a female Schaus swallowtail in Biscayne National Park on Elliott Key, the first capture of a female since a multi-agency work group got a permit to do so last year. The Schaus population has declined so much that last year the U.S. Fish and Wildlife Service (Service) issued UF an emergency permit to collect eggs. That effort ended without a single female sighting last summer but got off to a promising ...

LAST 30 PRESS RELEASES:

Drones reveal extreme coral mortality after bleaching

New genetic finding uncovers hidden cause of arsenic resistance in acute promyelocytic leukemia

Native habitats hold the key to the much-loved smashed avocado’s future

Using lightning to make ammonia out of thin air

Machine learning potential-driven insights into pH-dependent CO₂ reduction

Physician associates provide safe care for diagnosed patients when directly supervised by a doctor

How game-play with robots can bring out their human side

Asthma: patient expectations influence the course of the disease

UNM physician tests drug that causes nerve tissue to emit light, enabling faster, safer surgery

New study identifies EMP1 as a key driver of pancreatic cancer progression and poor prognosis

XPR1 identified as a key regulator of ovarian cancer growth through autophagy and immune evasion

Flexible, eco-friendly electronic plastic for wearable tech, sensors

Can the Large Hadron Collider snap string theory?

Stuckeman professor’s new book explores ‘socially sustainable’ architecture

Synthetic DNA nanoparticles for gene therapy

New model to find treatments for an aggressive blood cancer

Special issue of Journal of Intensive Medicine analyzes non-invasive respiratory support

T cells take aim at Chikungunya virus

Gantangqing site in southwest China yields 300,000-year-old wooden tools

Forests can’t keep up: Adaptation will lag behind climate change

Sturgeon reintroduction initiative yields promising first-year survival rate

Study: Babies’ poor vision may help organize visual brain pathways

Research reveals Arctic region was permafrost-free when global temperatures were 4.5˚ C higher than today

Novel insights into chromophobe renal cell carcinoma biology and potential therapeutic strategies

A breakthrough in motor safety: AI-powered warning system enhances capability to uncover hidden winding faults

Research teases apart competing transcription organization models

Connect or reject: Extensive rewiring builds binocular vision in the brain

Benefits and risks: informal use of antibiotics to prevent sexually transmitted infections on the rise in key populations in the Netherlands

New molecular tool sheds light on how cancer cells repair telomeres

First large-scale stem cell bank enables worldwide studies on genetic risk for Alzheimer’s disease

[Press-News.org] Singapore research team identifies new drug target in deadly form of leukemia