Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene expression profiles predict survival of lymphoma patients after chemotherapy

20.06.2002


Patterns of genes that are active in tumor cells can predict whether patients with diffuse large B-cell lymphoma (DLBCL) are likely to be cured by chemotherapy, scientists reported today in the New England Journal of Medicine.

Researchers analyzed thousands of genes in lymphoma biopsy samples from patients with DLBCL and determined that the activity of as few as 17 genes could be used to predict patients’ response to treatment. "We’re able to reliably predict the survival of these patients using data from a small number of genes, indicating that this technique should be entirely manageable for routine use," said National Cancer Institute (NCI) investigator Louis M. Staudt, M.D, Ph.D., the senior author on the study.

DLBCL is the most common type of non-Hodgkin’s lymphoma in adults. Approximately 16,000 new cases are diagnosed in the United States each year, and standard chemotherapy for the disease is effective in only 40 percent of patients. Profiling gene expression in patients’ tumors may help clinicians decide which patients are suitable candidates for standard therapy and which should consider other options for treatment.



The discovery of the predictive genes relied on DNA microarray technology, which allows researchers to determine which genes are active within cells. Microarrays, also known as gene chips, are glass slides that have been coated with thousands of spots of DNA, each representing a different gene. When a gene is active in a cell, it produces RNA copies known as transcripts. To measure the activity of genes, researchers use the RNA transcripts to make a fluorescent gene probe. When these gene probes are allowed to bind to their corresponding DNA spot on the chip, those spots on the chip light up. Scientists use the pattern and intensity of light emitted to determine the activity of each of the chip’s thousands of genes.

For this study, researchers used the Lymphochip, a specialized microarray containing 12,000 DNA spots representing genes expressed in normal and malignant lymphoid cells. Developed as part of the NCI’s Cancer Genome Anatomy Project, the Lymphochip is particularly useful for finding differences in gene expression among lymphoid cancers.

Staudt and his colleagues profiled gene expression in 240 tumor biopsies from patients with DLBCL and identified more than 600 genes whose expression varied significantly between patients who had responded well to treatment and those whose response was poor. These genes highlight aspects of the tumors that affected response to therapy, including how fast tumor cells were dividing and from what type of normal lymphocyte (a type of white blood cell) the tumor originated. Many of the predictive genes suggest that a patient’s immune response to the tumor is important for achieving a cure with chemotherapy.

Focusing on genes where the difference in expression was most dramatic between the two groups of patients, researchers narrowed the key genes down to 17. From these genes, the investigators created a formula that could be used to predict survival following chemotherapy. This predictor classified the patients into four groups of equal size. The five-year survival rates for these groups were 73 percent, 71 percent, 34 percent, and 15 percent.

Currently, physicians rely on the International Prognostic Index (IPI) to evaluate patients with DLBCL. This predictive index is based on clinical factors including age, stage of the tumor, and the presence of disease that has spread outside the point of origin. While useful for some purposes, Staudt noted that the IPI has not been successful in identifying the best candidates for alternate therapies. "Based on variations in gene expression, we can now do a better job of predicting patient outcomes," he said.

As an example, Staudt explained that 32 of the 240 patients in this study were classified in the group with the poorest prognosis according to the IPI. Of these, four were in fact cured by standard chemotherapy. Gene expression profiling successfully identified each of these.

For those that don’t respond to chemotherapy, alternatives are available. "For half of the patients with diffuse large B-cell lymphoma, conventional chemotherapy appears to be a reasonable option, but for patients in the poor-risk group, we have to consider other therapies," Staudt said. One possibility for some patients would be a bone marrow transplant. There are also numerous clinical trials for which these patients may be eligible.

One option is PS-341, a new agent that targets a pathway in the cell that blocks chemotherapy. Gene expression profiling revealed that in DLBCL patients who do not respond well to standard chemotherapy, lymphoma cells have activated this pathway, known as NF-kB. Based on these results, a Phase II clinical trial of PS-341 along with standard chemotherapeutic agents is planned to begin later this year at NCI and other institutions. Blocking the NF-kB signaling pathway with PS-341 will allow DLBCL tumor cells to die more readily, which researchers hope will improve patient survival. This trial will enroll DLBCL patients who have relapsed after standard chemotherapy. Gene expression profiles of the patients’ tumors will be determined prior to treatment to understand which patients respond best to this new regimen.

Trials designed to correlate clinical results with molecular data will allow researchers to identify drugs that are effective in subgroups of cancer patients, an approach that has already proven effective in finding new agents to treat breast cancer and leukemia. Staudt said gene profiling will make it possible to obtain more information from clinical trials in the future. "It makes sense to get the maximum amount of information from patients’ valuable participation in clinical trials," he said. "It’s a better investment in the research for both doctors and patients."


This research was sponsored by NCI as part of the Lymphoma/Leukemia Molecular Profiling Project and the NCI Director’s Challenge. The participating institutions included the University of Nebraska Medical Center, Omaha; the British Columbia Cancer Agency, Vancouver; the Norwegian Radium Hospital, Oslo; the University of Wuerzburg, Germany; the University of Barcelona, Spain; the Southwest Oncology Group; and the NCI Center for Cancer Research, Bethesda, Md.

NCI Press Office | EurekAlert!
Further information:
http://cancer.gov/clinical_trials/
http://www.cancer.gov

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>