Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Acute lymphoblastic leukaemia: A new drug class in cancer therapy

30.10.2019

Acute lymphoblastic leukaemia (ALL) is a rare form of cancer that commonly affects children, mostly under the age of five years. In the search for new therapeutic options, researchers at Vetmeduni Vienna have now discovered a new mechanism of the disease process and have developed a novel drug treatment line that is pioneering for future cancer therapies. The groundbreaking study was recently published in Nature Communications.

During their search for new therapeutic options for acute lymphoblastic leukaemia (ALL), a team of researchers at Vetmeduni Vienna have discovered a new function for a special enzyme, cyclin-dependent kinase 8 (CDK8), as part of the signalling system in ALL.


Concept of a dual degrader

Ingeborg Menzl/Vetmeduni Vienna

Most important for future therapies is the presence of a therapeutic window: healthy blood cells are not affected by the absence of CDK8, while the leukaemic cells need CDK8 to survive.

Using leukaemia mouse models, first author Ingeborg Menzl from the Institute of Pharmacology and Toxicology at Vetmeduni Vienna and her colleagues demonstrated that CDK8-deficient leukaemia cells show an increase in cell death.

“Of note is that the function of CDK8 in ALL is independent of enzymatic activity, which means that conventional kinase inhibitors are ineffective,” says Menzl. Based on this finding, the research team asked for potential interaction partners and discovered a previously unknown link between CDK8 and the mTOR signalling pathway in cancer cells.

Dual degrader – a therapy line with combined effect

In collaboration with the research team of Nathanael Gray from the Harvard Medical School, the researchers used a new generation of drugs that do not block enzymatic activity but induce the degradation of proteins (called PROTACs). In this way, it was possible to kill two birds with one stone, as senior author Veronika Sexl, the director of Institute of Pharmacology and Toxicology at Vetmeduni Vienna, explains:

“Using a newly synthesized PROTAC, a small molecule we have called YKL-06-101, mTOR signalling is blocked while simultaneously degrading CDK8. This represents a novel therapeutic line in drug development: a single drug is enough to degrade one molecule, CDK8, while simultaneously blocking a signalling pathway enzymatically.” With this concept of a dual degrader, the researchers are pioneering for future cancer therapies.

A complement to the drugs currently in use

Acute lymphoblastic leukaemia (ALL) is caused by an uncontrolled proliferation of immature lymphocytes. This, in turn, can be caused by genetic alterations resulting in gene products such as the oncoprotein BCR-ABL.

Although patients have benefited from the development of imatinib, a tyrosine kinase inhibitor, relapses occur. To guarantee therapeutic improvements it is essential to understand how the oncoprotein BCR-ABL affects cell signalling. The present study by Vetmeduni Vienna is an important contribution in this direction.

Service:
The article “A kinase-independent role for CDK8 in BCR-ABL1+ leukemia” by Ingeborg Menzl, Tinghu Zhang, Angelika Berger-Becvar, Reinhard Grausenburger, Gerwin Heller, Michaela Prchal-Murphy, Leo Edlinger, Vanessa M. Knab, Iris Z. Uras, Eva Grundschober, Karin Bauer, Mareike Roth, Anna Skucha, Yao Liu, John M. Hatcher, Yanke Liang, Nicholas P. Kwiatkowski, Daniela Fux, Andrea Hoelbl-Kovacic, Stefan Kubicek, Junia V. Melo, Peter Valent, Thomas Weichhart, Florian Grebien, Johannes Zuber, Nathanael S. Gray and Veronika Sexl was published in Nature Communications.
https://www.nature.com/articles/s41467-019-12656-x

About the University of Veterinary Medicine, Vienna:
The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms. The Vetmeduni Vienna plays in the global top league: in 2019, it occupies the excellent place 5 in the world-wide Shanghai University veterinary in the subject "Veterinary Science". http://www.vetmeduni.ac.at

Wissenschaftliche Ansprechpartner:

Ingeborg Menzl 
Institute of Pharmacology and Toxicology
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-2900
Ingeborg.Menzl@vetmeduni.ac.at

Originalpublikation:

https://www.nature.com/articles/s41467-019-12656-x

Weitere Informationen:

https://www.vetmeduni.ac.at/en/infoservice/press-releases/press-releases-2019/ac...

Nina Grötschl | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Helping hands from within: Live-in bacteria protect plants against infections
04.11.2019 | Netherlands Institute of Ecology (NIOO-KNAW)

nachricht Lymphatic system found to play key role in hair regeneration
04.11.2019 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Memory Effect at Single-Atom Level

An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.

The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.

Im Focus: Shedding new light on the charging of lithium-ion batteries

Exposing cathodes to light decreases charge time by a factor of two in lithium-ion batteries.

Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...

Im Focus: Visible light and nanoparticle catalysts produce desirable bioactive molecules

Simple photochemical method takes advantage of quantum mechanics

Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...

Im Focus: An amazingly simple recipe for nanometer-sized corundum

Almost everyone uses nanometer-sized alumina these days - this mineral, among others, constitutes the skeleton of modern catalytic converters in cars. Until now, the practical production of nanocorundum with a sufficiently high porosity has not been possible. The situation has changed radically with the presentation of a new method of nanocorundum production, developed as part of a German-Polish cooperation of scientists from Mülheim an der Ruhr and Cracow.

High temperatures and pressures, processes lasting for even dozens of days. Current methods of producing nanometer-sized alumina, a material of significant...

Im Focus: Structured light promises path to faster, more secure communications

Quantum mechanics is embracing patterns of light to create an alphabet that can be leveraged to build a light-based quantum network

Structured light is a fancy way to describe patterns or pictures of light, but deservedly so as it promises future communications that will be both faster and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

 
Latest News

NTU Singapore researchers create quantum chip 1,000 times smaller than current setups

04.11.2019 | Information Technology

Sheffield scientists identify new potential treatment pathway for cardiovascular disease

04.11.2019 | Health and Medicine

A plethora of states in magic-angle graphene

04.11.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>