Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene that is crucial for antibody-producing cell development is key to blood cell cancer

28.08.2003


Finding that an abnormally active Bcl10 gene drives B cells to become cancerous suggests blocking the gene would be an effective treatment for MALT lymphoma



A gene that is crucial to the development and function of an entire family of immune cells is also key to understanding why one member of that family can become cancerous. Investigators at St. Jude Children’s Research Hospital and the Blood Research Institute at the Blood Center of Southeastern Wisconsin, Milwaukee, reported this finding in the September 2003 issue of Nature Immunology.

The St. Jude researchers had previously shown that one of these cell types, marginal-zone B cells, can give rise to a cancer called mucosa-associated lymphoid tissue (MALT) lymphoma when the cells abnormally over-express a gene called Bcl10. The current finding suggests that a drug that blocks the action of Bcl10 could be an effective treatment for this cancer.


The researchers discovered that Bcl10 activates a pathway of molecular signals that drives antibody-producing B cells to mature into one of three different members of this family of immune system cells: follicular, marginal zone and B1 B cells. Mice lacking Bcl10 have a significant decrease in mature B cells and cannot launch an effective antibody response against bacteria in their bloodstream.

To learn how Bcl10 controls B cell development and function, the investigators studied mice in which the gene was inactivated. The mice produced nearly normal numbers of immature B cells. However, these cells did not mature normally. This showed that Bcl10 function is essential for B-cell development.

The researchers found that mice lacking a functional Bcl10 gene could not activate specific pathways of signaling molecules that belong to a family of proteins called NF-êB. The NF-êB proteins are normally activated by Bcl10 after B cells encounter invading organisms, such as bacteria. These proteins then cause B cells to fully mature and release antibodies targeted against those specific organisms.

The central role of Bcl10 in B cell development and function is further evidence that this gene is a major contributor to the development of MALT lymphoma, according to St. Jude scientist Liquan Xue, Ph.D., the article’s lead author.

"When Bcl10 jumps to a new location in a chromosome due to a genetic abnormality known as a rearrangement, it lands next to a section of DNA that forces the gene to be continually active," Xue said. "Bcl10 then continually activates the NF-êB proteins, driving the marginal-zone B cells to keep replicating themselves. That continual proliferation of the B cells leads to MALT lymphoma."

Demin Wang, an associate investigator at the Blood Research Institute, is the senior author of the article. He headed the work done at that location.

"Our discovery of the roles of Bcl10 in the development and functioning of B cells brings us a step closer to understanding how to control its activity and cure MALT lymphoma," Wang said. He is also an assistant professor at the Model Animal Research Center in Nanjing University, China, and at the Medical College of Wisconsin in Milwaukee.

The researchers also tested the ability of LPS, a molecule that forms part of the walls of some infectious bacteria, to stimulate marginal-zone B cells to multiply--a normal part of the body’s infection response. Located mainly in the spleen, marginal-zone B cells usually multiply after binding with the LPS in bacteria, increasing the numbers of B cells releasing antibodies. In mice lacking the Bcl10 gene, however, LPS failed to stimulate B cells to proliferate normally. This observation showed that the gene is required for this type of B cell to respond to infections.

Mice lacking Bcl10 genes were infected with a strongly disease-causing strain of Streptococcus pneumoniae, which causes one of the most common forms of pneumonia in humans. Unable to clear up the infection, these mice died. However, mice with normal Bcl10 genes mounted immune responses to the infection and survived.

"This study is an example of how basic research can hold the promise of tangible benefits to people suffering from a particular disease," said Stephan Morris, M.D., an associate member of the St. Jude Pathology and Hematology-Oncology departments and one of the article’s authors. Morris, one of the discoverers of Bcl10, initiated the current studies and directed the work at St. Jude.


###
Other authors of the study include Carlos Orihuela, Elaine Tuomanen, and Xiaoli Cui (St. Jude); and Renren Wen (Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee).

St. Jude Children’s Research Hospital St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit http://www.stjude.org.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>