Important protein for leukaemia treatment discovered
(Vienna, 09 February 2011) Researchers at the MedUni Vienna have revealed a direct link between the protein STAT5 and the emergence of leukaemia cells, which can develop antibiotic resistance. These insights make new therapy approaches possible and can be used to improve existing treatments.
Every year, around 25,000 people worldwide die from chronic myeloid leukaemia (CML), generally the result of a genetic defect (‘Philadelphia Chromosome’). Whilst there is still no cure for the disease, a well-tolerated treatment has been around for approximately ten years, which involves a daily dosage of the drug ‘imatinib’ and can at least delay the progression of the leukaemia. However, since the tumour cells develop resistance over the course of the disease, the dosage must regularly be increased, but this is only possible up to a certain point (a maximum of double the dosage), otherwise this produces severely harmful side-effects. The recent study by the MedUni Vienna has now shed light on one of the causes for the development of this resistance.
Using mice and human cells, Professor Veronika Sexl MD from the Centre for Physiology and Pharmacology at the MedUni Vienna and her team have been able to demonstrate that there is a direct link between the emergence of the protein STAT5 and the tumour cells. As such, imatinib resistance of leukaemia cells increases as levels of the STAT5 protein rise. Conversely, if there is a complete absence of STAT5 proteins, the tumour cells cannot survive. Consequently, the STAT5 protein does not just represent an important marker for the ability to diagnose the progress of the disease, it may also make it possible to develop a drug, which inhibits or prevents the production of STAT5 – a form of therapy that would eliminate the resistance of the tumour cells and could always be effective with the same dosage. It is unclear at present whether the stem cells, which caused the disease and have become immune to the drug, could also be killed.
In any case, the discovery of this link is an important step forward for research into new therapy approaches in relation to the second-most prevalent form of chronic leukaemia. The study was the result of close cooperation between university lecturer Dr. Richard Moriggl from the Ludwig Boltzmann Institute for Cancer Research and the team headed up by Associate Professor Dr. Peter Valent (from the Clinical Division of Haematology and Haemostaseology, University Department for Internal Medicine I at the MedUni Vienna and the Ludwig Boltzmann Cluster for Oncology). Thanks to its relevance, the work has been published in the internationally renowned journal Blood.
» Publication in “Blood”:
High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia
Wolfgang Warsch, Karoline Kollmann, Eva Eckelhart, Sabine Fajmann, Sabine Cerny-Reiterer, Andrea Hölbl, Karoline V Gleixner, Michael Dworzak, Matthias Mayerhofer, Gregor Hoermann, Harald Herrmann, Christian Sillaber, Gerda Egger, Peter Valent, Richard Moriggl and Veronika Sexl
Blood First Edition Paper; DOI 10.1182/blood-2009-10-248211