Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumor cells' inner workings predict cancer progression

30.07.2012
Molecular markers help reveal nature of chronic lymphocytic leukemia -- slow or fast

Using a new assay method to study tumor cells, researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center have found evidence of clonal evolution in chronic lymphocytic leukemia (CLL).

The assay method distinguishes features of leukemia cells that indicate whether the disease will be aggressive or slow-moving, a key factor in when and how patients are treated.

The findings are published in the July 26, 2012 First Edition online issue of Blood.

The progression of CLL is highly variable, dependent upon the rate and effects of accumulating monoclonal B cells in the blood, marrow, and lymphoid tissues. Some patients are symptom-free for years and do not require treatment, which involves the use of drugs that can cause significant side effects and are not curative. In other patients, however, CLL is relatively aggressive and demands therapeutic intervention soon after diagnosis.

"Our study shows that there may not be a sharp dividing line between the more aggressive and less aggressive forms of CLL," said Thomas J. Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research and senior author of the study. "Instead, it seems that over time the leukemia cells of patients with indolent disease begin to use genes similar to those that are generally used by CLL cells of patients with aggressive disease. In other words, prior to requiring therapy, the patterns of genes expressed by CLL cells appear to converge, regardless of whether or not the patient had aggressive versus indolent disease at diagnosis."

Existing markers for aggressive or indolent disease are mostly fixed and have declining predictive value the longer the patient is from his or her initial diagnosis. When the blood sample is collected, these markers cannot reliably predict whether a CLL patient will need therapy soon, particularly when the patient has had the diagnosis of CLL for many years.

Kipps and colleagues studied thousands of genes, particularly those that code for proteins, in a group of 130 CLL patients with varying risks of disease progression. They identified 38 prognostic subnetworks of interacting genes and proteins that, at the time of sample collection, indicate the relative the aggressiveness of the disease and predict when the patient will require therapy. They confirmed their work using the method on two other, smaller CLL patient cohorts in Germany and Italy.

The subnetworks offer greater predictive value because they are based not on expression levels of individual genes or proteins, but on how they dynamically interact and change over time, influencing the course of the CLL and patient symptoms.

"In a sense, we looked at families rather than individuals," said Kipps. "If you find in an interconnected family where most genes or proteins are expressed at higher levels, it becomes more likely that these genes and proteins have functional significance."

He added that while the subnetworks abound in data, their complexity actually makes them easy to interpret and understand. "It's like when you look out of a window and see the sky, clouds, trees, people, cars. You're getting tremendous amounts of information that individually doesn't tell you much. But when you look at the scene as a whole, you see patterns and networks. This work is similar. We're taking all of the individual gene expression patterns and making sense of them as a whole. We're more able to more clearly see how they control and regulate function."

The findings help define how CLL – and perhaps other cancers – evolve over time, becoming more aggressive and deadly. "It's as if each tumor has a clock which determines how frequently it may acquire the chance changes that make it behave more aggressively. Although the rates can vary, it appears that tumors march down similar pathways, which converge over time to a point where they become aggressive enough to require therapy."

The study may alter how scientists think about CLL and how clinicians treat the disease: whether it is better to wait for later stages of the disease when tumor cells are more fragile and easier to kill, or treat early-stage indolent tumor cells aggressively, when they are fewer in number but harder to find and more resistant to therapy.

Co-authors are Han-Yu Chuang and Trey Ideker, Bioinformatics and Systems Biology Program, Department of Bioengineering, Department of Medicine, Moores Cancer Center, all at UCSD; Laura Rassenti, Department of Medicine and Moores Cancer Center, UCSD; Michelle Salcedo, Division of Biological Science, UCSD; Kate Licon, Department of Bioengineering and Department of Medicine, UCSD; Alexander Kohlmann, Roche Molecular Systems, Inc.; Torsten Haferlach, MLL Munchner Leukamielabor GmbH, Germany; and Robin Foa, Division of Hematology, University "La Sapienza," Italy.

Funding for this research came, in part, from National Science Foundation grant NSF425926, National Institutes of Health grant ES14811, Pfizer and Agilent laboratories. Additional support came from NIH grants for the CLL Research Consortium (P01-CA081534), a Merit Award to Kipps and trainee research award to Chuang from the American Society of Hematology.

About Chronic Lymphocytic Leukemia

CLL is the most common form of leukemia, and most commonly diagnosed in adults after the age of 50. Incidence rates increase with age. The majority of CLL patients are men. Roughly 16,000 Americans are diagnosed with the disease each year; 4,400 die from the disease annually. CLL is currently considered incurable, but typically progresses slowly with no ill effect. Treatment is often postponed until serious symptoms appear that affect quality of life.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>