Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Driving tumour cells to their death

24.03.2015

Researchers from the University of Freiburg help discover a new approach to treating B cell acute lymphoblastic leukaemia

B cell acute lymphoblastic leukaemia, or B-ALLis the most common tumour disease in children and also occurs in adults. It develops when signalling pathways in immature B cells, or pre-B cells, are dysregulated. Prof. Dr. Markus Müschen from the University of California in San Francisco, USA, and his team worked together with the BIOSS researchers Prof. Dr. Hassan Jumaa and Prof. Dr. Michael Reth to find a new approach for treating the B-ALL tumour disease. Their studies could change the way we think about clinical therapies for treating these tumour diseases. The scientists have published their research in the journal Nature.


Please see the article

B cells are white blood cells that produce antibodies against antigens, namely substances which the immune system recognises as foreign. Normal B cell development and maturation is regulated by a balance between kinase and phosphatase enzymes. These enzymes phosphorylate or de-phosphorylate the signalling subunits of the B cell antigen receptors (BCR).

This means that the kinases add phosphate groups to the BCR, while the phosphatases remove them. Only if it has been phosphorylated by kinases is a BCR completely active and signals to the B cell that there is a foreign substance. This means that the kinases and phosphatases affect the receptor’s capacity to send signals.

In B-ALL tumour cells, certain kinase enzymes, such as the Abelson tyrosine kinase (ABL), are altered and act as oncogenes, spurring the growth of tumours independently of the BCR. The B cells then continue to divide although they do not function. That is why this disease is treated with agents that inhibit the ABL kinase. However, resistant ABL mutants still often develop and the tumour continues to grow.

The American and German team investigated how BCR signalling in tumour cells is regulated. They discovered that the signalling subunits of the BCR in B-ALL tumour cells are hardly phosphorylated and that there is a higher number of inhibiting receptors on the cell’s surface. Because these receptors bind phosphatases, they prevent the BCR from becoming active. When the researchers shut off the inhibiting receptors or the associated phosphatases, the B-ALL tumour cells died instantly.

The researchers were also able to demonstrate in an animal experiment how a phosphatase inhibitor prevented tumours from spreading. By inhibiting the phosphatases, they essentially freed the BCR signalling pathways that the ABL kinase had been supressing. Because a B cell that has a disproportionate amount of active BCR receptors no longer has a balance of kinases and phosphatases, this form of therapy thus leads to cell death, or what is known as apoptosis.

Future ALL treatments could aim at inhibiting the phosphatases instead of the ABL kinases and thereby strengthen BCR signals. Reth said, "In the last few years, we have investigated at BIOSS the significance of the balance between kinases and phosphatases for the normal development of B lymph nodes. Now we’ve discovered that this also plays a role in the development and treatment of B cell tumours.”

Reth is the scientific director of the cluster of excellence BIOSS Centre for Biological Signalling Studies. He is also a professor at the Institute of Biology III at the University of Freiburg and head of a research group at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. Jumaa is now a professor at the Institute of Immunobiology at the University of Ulm and was a member of the BIOSS Centre for Biological Signalling Studies.

Original Publication:

Zhengshan Chen, Seyedmehdi Shojaee, Maike Buchner, Huimin Geng, Jae Woong Lee, Lars Klemm, Björn Titz, Thomas G. Graeber, Eugene Park, Ying Xim Tan, Anne Satterthwaite, Elisabeth Paietta, Stephen P. Hunger, Chery L Willman, Ari Melnick, Mignon L Loh, Jae U. Jung, John E. Coligan, Silvia Bolland, Tak W. Mak, Andre Limnander, Hassan Jumaa, Michael Reth, Arthur Weiss, Clifford A. Lowell and Markus Müschen (2015). Signaling thresholds and negative B cell selection in acute lymphoblastic leukemia. Nature. DOI: 10.1038/nature14231


Contact:
Prof. Dr. Michael Reth
BIOSS Centre for Biological Signalling Studies
University of Freiburg
Phone: +49 (0)761 / 203 - 97663
E-Mail: michael.reth@bioss.uni-freiburg.de

Rudolf-Werner Dreier | University of Freiburg
Further information:
https://www.pr.uni-freiburg.de/pm/2015/pm.2015-03-24.42-en?set_language=en

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

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....

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

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

Computer model predicts how fracturing metallic glass releases energy at the atomic level

20.07.2018 | Physics and Astronomy

Relax, just break it

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>