Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New gene marker may identify need for intense AML therapy

15.11.2005


Researchers here have discovered a new marker that might identify a serious form of acute myeloid leukemia (AML) in people who lack the signs that normally alert doctors that the patient needs intense therapy.



The study was led by researchers with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. It focused on AML patients whose cancer cells show none of the chromosome alterations that help doctors determine the probable prognosis and the best potential treatment for many people with acute leukemia.

Specifically, the study examined the activity of a gene known as ETS-Related Gene (ERG) in AML cells from these patients.


The findings, published online in the Journal of Clinical Oncology, suggest that when AML cells show high ERG activity, it signals an aggressive form of cancer that requires intense therapy, such as a stem-cell transplant from a matched donor.

Importantly, the study also showed that effects of ERG activity on disease relapse and long-term survival are influenced by the activity levels of other genes.

Last, the study suggests that ERG plays an important role in AML development and could provide a new target for future AML therapy.

The findings come from a Cancer and Leukemia Group B (CALGB) study led by Clara D. Bloomfield, professor of internal medicine, the William G. Pace III Professor in Cancer Research, OSU Cancer Scholar and senior adviser to the OSU Cancer Program.

“This is another of only a few predictive molecular markers for adults with AML who have normal cytogenetics,” says Bloomfield, who led the research that identified the first molecular marker for AML in this group of patients. Normal cytogenetics refers to cells with normal-looking chromosomes.

“If confirmed, our findings should improve survival in these patients and spare those who now receive more intense therapy but don’t need it.”

About 55 percent of AML patients have cancer cells showing chromosome alterations at the time of diagnosis. Doctors rely on these alterations to help determine the best therapy for these patients and the likelihood of remission and cure.

But the cancer cells in about 45 percent of AML patients have normal-looking chromosomes, giving doctors few clues for choosing therapy. Overall about 40 percent of these patients are alive after five years following intensive therapy.

“This means that 60 percent of patients relapse,” Bloomfield says, “and that probably happens because those who relapse have unidentified gene mutations and molecular changes that affect survival and their response to treatment.

“Some examples of these mutations and molecular changes have already been identified. ERG is probably another, and I have no doubt that more will be found.”

The present study tested whether activity levels of ERG are related to remission and survival rates in AML patients with normal cytogenetics.

(Levels of gene activity, or more correctly, gene expression, refers to whether a gene is highly, moderately or not engaged in the production of a protein. Gene-expression levels are determined by measuring the number of RNA copies of the gene that are present in cells. A high number of RNA copies indicates a high level of gene activity; a low number indicates low gene activity.)

The study examined samples of cancer cells from 84 AML patients under age 60 years who had normal cytogenetics. The samples were analyzed for the activity levels of ERG and other genes known to influence treatment response in these patients.

The 84 samples were then divided into four groups according to ERG activity. The group with high ERG activity was compared with the other three groups combined in terms of the patients’ relapse and survival rates.

In general, the group with high ERG did extremely poorly compared with the other groups when consider by itself and in combination with other genes.

When the researchers looked at the likelihood of relapse and the influence of high ERG by itself, they found that 81 percent of high ERG patients relapsed after five years versus 33 percent of patients in the other groups.

However, when the risk of relapse was examined in combination with a second gene known as MLL PTD, patients with high ERG were four times more likely to relapse than the patients with low ERG..

When the researchers considered survival and the influence of ERG alone, they found that the group with high ERG lived an average of 1.2 years following treatment, while the other three groups had not yet reached their average survival when the study ended.

When the researchers then examined the impact of ERG in combination with other factors on survival, they found that the patients who did best had low ERG and low activity of a gene known as BAALC. Seventy percent of these patients were alive after five years.

“This study is important because we have found another gene (ERG) that seems to have a major influence in this large subset of AML patients,” Bloomfield says, “and we’ve identified other genes that alter ERG’s effects on relapse and survival.”

Overall, the evidence strongly indicates that ERG may play a key role in leukemia development. Therefore, a drug that is designed to reduce ERG activity, perhaps in combination with chemotherapy or other targeted therapy, “might prevent these patients from relapsing,” Bloomfield says, “and that would be quite a success.”

Other OSU researchers involved in this study were Guido Marcucci, Claudia D. Baldus, Amy S. Ruppert, Krzysztof Mrozek, Susan P. Whitman, Colin G. Edwards, Danilo Perrotti, Michael A. Caligiuri and Albert de la Chapelle.

Funding from the National Cancer Institute and The Coleman Leukemia Research Foundation supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>