Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new target for lymphoma therapy

10.12.2009
Gene enhancer is responsible for activating cancer-causing genes in B cells

Researchers at the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's Hospital Boston (PCMM/IDI) have found a link between a common mutation that can lead to cancer and a distant gene regulator that enhances its activity. Discovery of this relationship could lead to drugs targeting B-cell lymphomas, including Burkitt's lymphoma, an aggressive cancer in children, as well as multiple myelomas and other blood-related cancers.

Lymphomas often originate in B cells, the same cells that produce antibodies to help fight infections. A B cell can become cancerous if a gene known as c-myc leaps to another section of DNA (the IgH region, responsible for building antibodies), fuses with it, and somehow becomes over-activated. Scientists have wondered for years how this oncogenic activation occurs, in particular what component in the IgH region activates c-myc. The new study, published in the Dec. 10 issue of Nature, identifies this regulatory component, and marks the first time researchers are able to understand how this movement of genes, or "chromosomal translocation," can hijack a B cell's operation badly enough to lead to cancer.

"IgH-to-myc translocation is the classic example of activation of an oncogene in cancer," says Frederick Alt, PhD, scientific director of PCMM/IDI and senior author of the study. "But nobody really understood how it works."

Aberrant DNA translocations can occur during two different stages of a B cell's development: during a process known as VDJ recombination, when a progenitor B cell creates an antibody to fight a specific pathogen, or during class switch recombination, when a mature B cell gives its antibody a different strategy to fight infection (changing from an IgM to an IgG antibody, for example). Based on their past research , Alt and his colleagues decided to focus on one part of the IgH region called IgH 3' regulatory region (IgH3'RR). They had already shown IgH3'RR to be a far-reaching gene regulator that enhances the transcription of neighboring genes in the IgH region during class switch recombination.

To investigate the relationship between IgH3'RR and lymphoma, the team, led by Alt and first author Monica Gostissa, PhD, of PCMM/IDI, deleted the IgH3'RR in a line of mutant mice previously generated in the Alt lab. These mice routinely develop a B-cell lymphoma in which c-myc is translocated to the IgH region of the DNA. However, without IgH3'RR, mature B cells did not become cancerous, suggesting that mature B cells -- from which most human lymphomas originate -- need IgH3'RR in order to develop into lymphoma.

"The study shows that the IgH3'RR is a key element for turning on the cancer-causing activity of c-myc after it is translocated to the IgH locus," says Alt. He noted that the study also shows that the cancer-causing activity of the IgH3'RR on c-myc can extend over surprisingly long chromosomal distances.

The study suggests the IgH3'RR as a new target for arresting lymphomas and other blood-related cancers that arise from mature B cells. Though inactivating IgH3'RR can impair a B cell's versatility in creating different classes of antibodies, it would not leave a patient immune-deficient because the B cells would retain some of their activity, says Gostissa. Furthermore, such a treatment would be reversible.

The next step is for the researchers to see what eliminating IgH3'RR will do to existing tumors, and then to create a cell-based drug screening assay to test for possible IgH3'RR inhibitors.

The study was funded by grants from the National Institutes of Health and the Leukemia and Lymphoma Society of America (including funds from the de Villiers International Achievement Award). Alt is an investigator of the Howard Hughes Medical Institute.

Monica Gostissa, Catherine T. Yan, Julia M. Bianco, Michel Cogne, Eric Pinaud and Frederick W. Alt. "Long-range Oncogenic Activation of IgH/c-myc Translocations by the IgH 3' Regulatory Region."

Nature. Dec. 10, 2009.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 13 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.

Rob Graham | EurekAlert!
Further information:
http://www.childrenshospital.org/newsroom

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>