CeMM Identifies Inherited Susceptibility for a Blood Malignancy

Important discovery at the Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM): In cooperation with the Medical University of Vienna, CeMM scientists show that a common gene variant increases the risk of developing a certain type of blood malignancy. Carriers of the discovered gene variant are up to 6-fold more likely to develop a certain kind of cancer than noncarriers. This is the first time in cancer research that a gene variant is found to preferentially acquire a disease-causing mutation.

Vienna, 13 March 2009 - The Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM) announces the identification of a gene variant on chromosome 9 that increases the likelihood of acquiring a disease-causing mutation in this genomic region. The study was directed by Robert Kralovics, one of the Principal Investigators at CeMM and at the Division of Hematology and Blood Coagulation of the Medical University of Vienna (MUV). First author of the publication is Damla Olcaydu. The study provides the first evidence that a specific but common variant of the JAK2 gene is more susceptible to a mutation, and therefore confers a higher risk of developing myeloproliferative neoplasms (MPN) – blood diseases resembling chronic leukemia. The CeMM researchers made this discovery in collaboration with the Medical University of Vienna, namely with Heinz Gisslinger, Bettina Gisslinger and Ingrid Pabinger from the Department of Internal Medicine I, Division of Hematology and Blood Coagulation. The results will appear in the online advanced publication route of the journal Nature Genetics on Sunday, 15 March, together with the work of Nicholas C. P. Cross and his research group from the University of Southampton, Salisbury, UK who independently made the same discovery.

The JAK2 kinase is an enzyme that transfers signals from the cell membrane to the nucleus and regulates cell proliferation and survival. It is one of the key players in the regulation of blood production. In 2005, Robert Kralovics, while working in the group of Radek Skoda in Switzerland, contributed to the important discovery of a JAK2 gene mutation in about half of MPN patients. This mutation causes the JAK2 kinase to be constitutively active and results in overproduction of blood cells – a hallmark of MPN. The current investigations showed that the disease-causing JAK2 mutation preferentially occurs on one of the two common JAK2 gene variants present in the Western European population. At the General Hospital of Vienna (AKH), hundreds of patients with MPN are currently under treatment.

“Our latest finding, that a gene variant preferentially acquires a disease-causing mutation, is a phenomenon that has not been described in other blood cancers so far and is of major importance. This brings up a somewhat controversia hypothesis that DNA sequences can vary in their potential to acquire cancer-causing mutations. This differential mutagenesis of gene variants can explain certain cancer susceptibilities making our findings even more important” says Robert Kralovics.

Ulrich Jäger, Head of the Division of Hematology and Blood Coagulation, adds: “The cooperation with CeMM is very important for us. We are proud of the achievement that the group of Robert Kralovics made and are sure that more important discoveries will follow.”

CeMM scientific director Giulio Superti-Furga stresses: “We are happy that our strategic partnership with the MUV, in
particular with the Division of Hematology and Blood Coagulation, already shows such great results. We are all the more excited about moving into our new building in spring 2010. The facility will be located right in the center of the AKH campus and will therefore allow us to intensify the cooperation with our partners at the MUV.”

For further information please contact
Leopold Liechtenstein
CeMM Manager Public Relations & Sponsoring
Tel.: +43-1-40 160-70025
lliechtenstein@cemm.oeaw.ac.at

The following downloads and photos are provided on the CeMM website
http://www.cemm.oeaw.ac.at/?cont=downloads
Photo: CeMM Principal Investigator Robert Kralovics and first author Damla Olcaydu; Photo: CeMM Scientific Director Giulio
Superti-Furga; CVs: CeMM Scientific Director Giulio Superti-Furga and Principal Investigator Robert Kralovics; CeMM Research
Report 2007; CeMM Fact-Sheet; The publication will be accessible on the CeMM website on Monday, 16 March 2009.

For additional information also see the website of the Division of Hematology and Blood Coagulation at the Medical
University of Vienna: http://www.meduniwien.ac.at/haematology/
Publication (The publication will be accessible on the CeMM website on Monday, 16 March 2009)
A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Damla Olcaydu, Ashot Harutyunyan, Roland Jäger, Tiina Berg, Bettina Gisslinger, Ingrid Pabinger, Heinz Gisslinger, Robert Kralovics. Nature Genetics. DOI 10.1038/ng.341. published online by Nature Genetics on 15 March 2009

About CeMM

CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, is an international, independent and interdisciplinary research institute in molecular medicine. “From the clinic to the clinic”: Driven by medical needs, CeMM integrates basic research and clinical expertise to pursue innovative diagnostic and therapeutic approaches focused on cancer, inflammation and immune disorders. CeMM has six Principal Investigators recruited internationally and around 60 scientists. In 2010 CeMM will move into a new tailor-made building at the center of the Vienna General Hospital and in close proximity to research institutes of the Vienna Medical University providing space for 100 scientists. www.cemm.oeaw.ac.at

About the Austrian Academy of Sciences

The Austrian Academy of Sciences is the leading organization promoting non-university open source basic research in Austria.

The Academy gives new impetus by taking up new, forward-looking research areas. Scientific quality, innovation potential and sustainability are the main criteria for the Academy’s research profile. Currently the Academy is promoting about 66 research institutions, including three limited liability companies.

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