Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A discovery could be important for the therapy of lymphoma and leukemia

02.11.2010
The IRCM's Dr. Javier M. Di Noia identifies a mechanism regulating activation-induced deaminase

A recent scientific discovery made by researchers at the Institut de recherches cliniques de Montréal (IRCM) led by Dr. Javier Marcelo Di Noia, Director of the Mechanisms and Genetic Diversity research unit, was published online today by The Journal of Experimental Medicine.

The team identified a mechanism regulating activation-induced deaminase (AID), which could be important for the therapy of some types of lymphoma and leukemia.

AID is a B-lymphocyte enzyme that creates deliberate mutations in the DNA encoding antibodies, which helps produce an appropriate immune response. However, inappropriate expression of AID can also have harmful effects and lead to certain oncogenic (cancer-causing) mutations. When found in a tumour, uncontrolled levels of AID could increase the rate of gene mutation and, in turn, accelerate the progression of the disease.

"In studying the regulation of AID, we attempted to understand what restricts its access to the cell's nucleus," explains Alexandre Orthwein, doctoral student in Dr. Di Noia's research unit and first author of this study. "If we could control that aspect, we could prevent AID's negative mutating effects. We then discovered that Hsp90, one of the most abundant and vital proteins found in cells, stabilizes AID in the cytoplasm. Cytoplasmic AID is in fact in a dynamic equilibrium regulated by Hsp90."

By stabilizing AID, Hsp90 determines the enzyme's overall expression levels, which correlate with the extent of its physiological functions. Hence, Hsp90 assists AID-mediated antibody diversification. A number of Hsp90 inhibitors being commercially available, the researchers found that Hsp90 inhibition destabilizes AID, thus resulting in a proportional reduction in antibody gene diversification. Moreover, since AID levels also correlate with its pathological side effects, Hsp90 inhibition prevents uncontrolled off-target mutation by AID.

"We showed that inhibiting Hsp90 with known drugs, which are also currently used in clinical trials for the treatment of certain cancers, significantly reduces the amount of AID and, consequently, prevents this enzyme's undesired activity on DNA," adds Dr. Di Noia. "This regulatory mechanism determines the functional levels of AID in normal B cells and B cell lymphoma lines. So, Hsp90 inhibition provides the first pharmacological means to regulate AID expression and activity, which could be relevant for the therapy of some types of lymphoma and leukemia."

Dr. Di Noia, along with the IRCM's Technology Transfer Office, is currently taking the necessary steps to patent the proposed application of the Hsp90 inhibitors with the Canadian Intellectual Property Office (CIPO) and the United States Patent and Trademark Office (USPTO). These patent applications, promoted and commercialized by Univalor, cover the use of the AID biomarker in the selection of a cancer-fighting therapy. In the context of this technology, the treatment using an Hsp90 inhibitor targets tumours expressing AID, and consists of the administration of predetermined doses of the inhibitor in accordance with the expression levels of AID in the tumours.

According to The Leukemia & Lymphoma Society of Canada, one person is diagnosed with a blood cancer every four minutes and someone dies from a blood cancer every 10 minutes. This statistic represents over 54,000 people per year. In 2010, about 628,415 people are living with lymphoma or are in remission.

This research project was supported by the Canadian Institutes of Health Research (CIHR). "CIHR is proud to support the type of innovative research that Dr. Javier Marcelo Di Noia and his team are engaging in," says Dr. Morag Park, Scientific Director for CIHR's Institute of Cancer Research. "An understanding of the mechanisms that regulate activation-induced deaminase by heat shock protein 90 (Hsp90) will provide potential new therapies to treat some types of leukemia and lymphoma." The project also received support from the Cancer Research Society (CRS) and the Canada Research Chair program. In addition, Alexandre Orthwein holds a Cole Foundation doctoral fellowship.

Other researchers contributed to the study, including Anne-Marie Patenaude, research assistant in Dr. Di Noia's laboratory, El Bachir Affar from the Hôpital Maisonneuve-Rosemont, Alain Lamarre from the INRS-Institut Armand-Frappier research centre, and Jason C. Young from McGill University.

For more information, please refer to the online article summary published by The Journal of Experimental Medicine. The print publication will be available on November 22, 2010

Julie Langelier | EurekAlert!
Further information:
http://www.ircm.qc.ca

Further reports about: AID CIHR Canadian Light Source Cancer DNA Medicine blood cancer

More articles from Life Sciences:

nachricht New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences

nachricht The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>