The use of carefully chosen animal models often underlies crucial medical advances. A perfect example is provided by the recent demonstration that a known drug, imatinib, can be used to treat a rare, but highly aggressive, type of lymphoma. The work was largely undertaken in the group of Dr. Lukas Kenner at the Ludwig Boltzmann Institute for Cancer Research and the Medical University of Vienna, with the support of Drs. Karoline Kollmann and Veronika Sexl at the University of Veterinary Medicine, Vienna, together with a number of national and international collaborators. The findings were published online on October 14, 2012 in Nature Medicine. So-called anaplastic large cell lymphoma (ALCL) is even less attractive in real life than it is on paper. It is a highly aggressive type of lymphoma that generally occurs in children and young adults and that has, to date, proven extremely difficult to treat. It has long been known that ALCL patients frequently show a genetic alteration (a translocation) that causes expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), a gene known to be capable of giving rise to cancer. But how the NPM-ALK gene works has so far remained largely a matter of conjecture. Working in a mouse model for lymphoma, Dr. Kollmann in Dr. Sexl’s group at the University of Veterinary Medicine, Vienna, and colleagues at the Ludwig Boltzmann Institute for Cancer Research and the Medical University of Vienna were able to show that the development of lymphoma is absolutely dependent on the “platelet-derived growth factor receptor B” (PDGFRB), a protein already associated with the growth of other types of tumors. The scientists demonstrated that the effect was direct, with NPM-ALK stimulating the production of the transcription factors JUN and JUNB, which bind to and activate the PDGFRB promoter.
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