As part of the 3rd International Conference on Cytokine Signaling in Cancer in Rhodes, Greece, the Travel Awards were again awarded this year. Two of the awards went to Sebastian Kollmann from the Institute of Pharmacology and Toxicology and Anna Orlova from the Department of Functional Cancer Genomics at Vetmeduni Vienna.

In the project "STAT5A and STAT5B in Hematopoietic and Leukemic Stem Cells - Between Death and Immortality", Sebastian Kollmann addresses the question of why mutations in lymphoma and leukemia patients are mainly found in STAT5B and hardly in the related protein STAT5A. It describes an important role for STAT5B in the self-renewal of hematopoietic and leukemic stem cells and thereby contributes with basic information to understand this question.

In the study “The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease”, Anna Orlova shows that the overactivation of ERBB receptors, and consequently also of STAT3, leads to the transferability of facial tumours among Tasmanian devils. The study also unravels that the cancer cells can be specifically targeted by drug inhibition of the ERBB receptor.

Tobias Suske is a PhD student in the group of Richard Moriggl at the Institute of Animal Breeding and Genetics, Vetmeduni Vienna. He was honored with the Young Investigator Award at the Annual Meeting of the OeGHO & AHOP in Linz AT for his excellent talk on “The gain-of-function STAT5BN642H mutation as a driver of T-cell lymphoma and leukemia”.

The Austrian Society for Haematology and Clinical Oncology (OeGHO, www.oegho.at) and the Working Group for Haematological and Oncological Nursing (AHOP, www.ahop.at) have been awarding outstanding research of young investigators since 2010. The award is € 1.000 and is donated by Janssen Cilag Pharma GmbH.


©OeGHO


©OeGHO

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 amino acid change in STAT5B makes it hyperactive and leads to T-cell cancer development. We have tackled the difficult task to visualize the structure and shape of STAT5B in order to facilitate the discovery of new drugs that specifically target the mutant cancer-causing form of the protein, whilst sparing the important normal-functioning STAT5B.

We 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 the atomic level. We also developed a new cancer mouse model driven by mutant STAT5B, which allows the study of one of the most aggressive T-cell cancers seen in patients. Importantly, the structural information and the disease model can now be used to test new drugs that target only the cancer-causing form of STAT5B, which will significantly reduce the side-effects and increase the effectiveness of the treatment.

Publication in Nature Communications

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†

*equal author contribution; †corresponding authorship

Structural and functional consequences of the STAT5BN642H driver mutation (2019); Doi: https://doi.org/10.1038/s41467-019-10422-7