Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Stanford diagnostic test for rare leukemia appears to give faster results

07.10.2008
A new twist on a well-known cell sorting technique may allow physicians to diagnose rare leukemias in hours instead of weeks, according to a study by researchers at the Stanford University School of Medicine and UC-San Francisco.

The clinical promise of the Stanford-developed approach, which eavesdrops on individual cells to decipher potentially dangerous molecular conversations, is likely to extend to many other disorders in which cell-signaling pathways are disrupted.

"We've eliminated a big bottleneck," said postdoctoral scholar Nikesh Kotecha, PhD, of the work. Kotecha, the lead author of the study, conducted the work as a graduate student in the laboratory of immunologist Garry Nolan, PhD, a co-senior author of the paper. "Now we can use this signaling assay to confirm a diagnosis much more quickly."

The study will be featured on the cover of the Oct. 7 issue of Cancer Cell. In addition to Nolan, who is an associate professor of microbiology and immunology as well as a member of Stanford's Cancer Center, the other senior co-author is Mignon Loh, MD, an associate professor of clinical pediatrics at UCSF.

"We couldn't have done this research without involving immunology, signaling biology, medicine, statistics and informatics," said Kotecha, who completed his PhD in biomedical informatics. "It's a true example of the strengths of translational research, bringing laboratory bench work and informatics to address a clinical problem."

The multidisciplinary technique builds on an experimental technique called flow cytometry, in which fluorescently labeled antibodies are used to classify and sort cells based on proteins displayed on their outer surface. The new approach, developed in Nolan's lab in 2004, creates small holes in the cell membrane prior to sorting. These holes allow other antibodies to enter the cell and bind to signaling molecules involved in the cell's internal monologue — in this case, a protein called STAT5. Kotecha and his collaborators used an antibody that binds only to the activated, or phosphorylated, version of the protein to determine the signaling status of the pathway in individual cells exposed to a variety of conditions.

The effect is somewhat like moving through an airport security line that screens travelers not just for weapons concealed outside their bodies, but also for their emotional states: "Happy to be headed home" in one line, "afraid of flying" in another and just plain "cranky" in another. Combine the two measurements — the availability of a weapon and the mood of the person carrying it — and you have a more reliable assessment of risk than with either one alone.

The researchers tested the technique's clinical value by applying it to the diagnosis of a difficult diagnostic problem: juvenile myelomonocytic leukemia, or JMML. Children with the relatively rare disorder typically have fevers, grow poorly, suffer from infections and generally look like they could have any one of a number of different diseases. A prompt diagnosis of JMML is particularly important because, unlike other leukemias, the only cure is a bone marrow transplant.

One of the few reliable indicators of JMML cells is their tendency to proliferate in response to very low levels of a growth-stimulating factor called GM-CSF; normal cells respond only at higher levels. But it can take two to three weeks to grow enough cells in the laboratory to get a definitive answer to this test.

Kotecha knew that GM-CSF activates a particular cellular signaling cascade called the JAK-STAT pathway. Although that pathway had not previously been directly implicated in JMML, Kotecha used an antibody that binds only to activated STAT5 to determine whether the cells of 12 patients with JMML displayed abnormally high levels of the protein in response to low doses of GM-CSF. Eleven of the 12 did so — confirming the involvement of the STAT pathway in the disorder.

"I was surprised how much more we can learn about the inner nature of these cells by 'interrogating' them with different conditions," said Nolan, who is also a member of the Donald E. and Delia B. Baxter Laboratory in Genetic Pharmacology at Stanford. "Time and again we are finding this to be a powerful amplifier of the fate of a diseased cell and a good way to understand why it responds to certain treatments and not others."

In contrast to the JMML samples, seven out of eight normal bone marrow samples, as well as eight out of eight samples from patients with similar, but not identical, disorders, maintained normal levels of activated protein after the low dose GM-CSF treatment — suggesting that the technique may be a sorely needed diagnostic aid for JMML.

The new technique also offers a way to monitor disease progress. With further refinement, the researchers hope that the technique can be used to screen the effectiveness of potential drugs for treatment of JMML and other disorders.

"Identifying populations of cells by their response to specific stimuli will facilitate our ability to assess the efficacy of specific agents in relevant subsets with increased precision," said Loh. "In an era of using increasingly sophisticated targeted agents, we hope that these studies will allow investigators to more fully appreciate the specificities of their therapies."

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Studies and Analyses:

nachricht Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)

nachricht The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Electrode materials from the microwave oven

19.10.2017 | Materials Sciences

New material for digital memories of the future

19.10.2017 | Materials Sciences

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>