21.06.2019: Every 35 seconds, a new patient is diagnosed with blood cancer. Although over the past 50 years treatments have improved and survival rates have increased dramatically for some types of blood cancers, many remain incurable. One such rare and aggressive type of blood cancer is formed when mutations occur in the DNA of an important immune cell, called a T-cell. These immune cells normally help the body fight off infection and cancer, but mutations can occur which cause T-cells to neglect their normal functions and grow uncontrollably. This often leads to a very aggressive and fatal blood cancer, which has not been well studied. Now, scientists have developed new strategies to understand better, how these mutations lead to T-cell cancer formation. This new informations are now used, to develop and test new drugs for cancer patients.

In a triple-effort between international research groups from the University of Veterinary Medicine Vienna, Harvard University and the University of Toronto, important new information was discovered about the protein STAT5B, which is mutated in patients with T-cell cancers. STAT5B, like all proteins, is made up of building blocks called amino acids. A single mutation, leading to a single amino acid change in STAT5B, can make it hyperactive and lead to increased T-cell growth. However, without being able to visualize the structure and shape of STAT5B, it is difficult for researchers to develop new drugs that target only the mutant cancer-causing form of the protein, whilst sparing the important normal-functioning STAT5B.

In a newly published study in Nature Communications, researchers have used a technique similar to medical X-rays to reveal for the first time the three-dimensional structures of normal and mutant STAT5B, down to an atomic level. Experiments and computer simulations using these structures have shown how this mutation causes small changes in the STAT5B protein shape, keeping it active for longer and allowing it to promote cancer. The researchers also developed a new important cancer mouse model driven by mutant STAT5B, which allows the study of one of the most aggressive T-cell cancers seen in patients. Importantly, this structural information and model can now be used to test new potential drugs that target only the cancer-causing form of STAT5B, which will significantly reduce the side-effects and increase the effectiveness of the treatment.

In addition to blood cancers, STAT5B has also been found to have important roles in many other cancer types. Therefore, these discoveries will also help scientists from all around the world to better understand and develop new drugs for patients with other forms of cancer.

The article „Structural and functional consequences of the STAT5BN642H driver mutation“ by Elvin D. de Araujo, Fettah Erdogan, Heidi A. Neubauer, Deniz Meneksedag-Erol, Pimyupa Manaswiyoungkul, Mohammad S. Eram, Hyuk-Soo Seo, Abdul K. Qadree, Johan Israelian, Anna Orlova, Tobias Suske, Ha T. T. Pham, Auke Boersma, Simone Tangermann, Lukas Kenner, Thomas Rülicke, Aiping Dong, Manimekalai Ravichandran, Peter J. Brown, Gerald F. Audette, Sarah Rauscher, Sirano Dhe-Paganon, Richard Moriggl and Patrick T. Gunning was published in Nature Communications.

_{This research was carried out with financial support by a private donation from Liechtenstein and it was also partly funded by the Austrian Science Fund (FWF; SFB-F4707, SFB-F06105), as well as an EU financed ERA PerMed Network grant.}